Sobetirome

updated

Sobetirome (GC-1, QRX-431) is a thyroid hormone receptor beta-selective research chemical with no FDA application located on 9 October 2026. In rats it lowered cholesterol about 30 times more potently than it induced tachycardia, and in monkeys it lowered cholesterol without tachycardia, but its fat loss was weaker than T3's. Two reviews state that phase 1 human trials were completed, no primary report was found, and both registered sobetirome studies were withdrawn with no participants.

Thyroid hormone receptor beta-selective thyromimetic

  • An openFDA query on 9 October 2026 found no FDA application for sobetirome, and GC-1 is also the name of a mouse cell line, which corrupts literature searches.
  • In cholesterol-fed rats, GC-1 lowered cholesterol about 30 times more potently than it induced tachycardia, and showed about 10-fold selectivity for metabolic rate over tachycardia.
  • In cynomolgus monkeys treated for 7 days, GC-1 lowered cholesterol and lipoprotein(a) with no tachycardia.
  • In a 6-week rat study, GC-1 reduced carcass fat by 15 to 23% against 14 to 74% for T3, while sparing skeletal muscle.
  • In mice, dosing at or above 10 micrograms per kg per day for 29 days depleted circulating T4 and T3 with normal TSH.
  • Both registered sobetirome studies were withdrawn with 0 participants, and two reviews state phase 1 was completed with no primary report found.

What is sobetirome, and is it approved?

Sobetirome (GC-1, QRX-431) is a thyroid hormone receptor beta-selective research chemical with no FDA application located on 9 October 2026. GC-1 is also the name of a mouse cell line, which corrupts literature searches.

Sobetirome is C20H24O4 (328.4 g/mol, CAS 211110-63-3, PubChem CID 9862248), with the synonyms GC-1 and QRX-431. A 2008 review by the investigator who made it describes it as a selective thyromimetic: a synthetic analog of thyroid hormone with tissue-specific actions, designed to bind thyroid hormone receptor beta over receptor alpha.

GC-1 is also the established name of a widely used mouse spermatogonial cell line, and a PubMed search on the bare string GC-1 returns mostly that cell line rather than this compound. A citation attributed to GC-1 has to be read for which GC-1 it means.

An openFDA Drugs@FDA exact brand-name and generic-name query for sobetirome returned no matching application on 9 October 2026. That supports the US-scoped statement that no FDA-approved sobetirome product was located.

PubChem CID 9862248: C20H24O4, 328.4 g/mol; GC-1 naming collision

Chemical identity record

National Library of Medicine. PubChem compound record CID 9862248 (sobetirome, GC-1, QRX-431).

Sobetirome: PubChem CID 9862248, C20H24O4, 328.4 g/mol, CAS 211110-63-3. Listed synonyms include GC-1 and QRX-431. GC-1 is also the established name of a widely used mouse spermatogonial cell line, and a PubMed search on the bare string GC-1 returns mostly that cell line rather than this compound. Any citation attributed to 'GC-1' has to be read for which GC-1 it means.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, no approved formulation
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
openFDA query, 9 October 2026: no sobetirome application returned

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA API query for brand name and generic name sobetirome, run on 9 October 2026.

An openFDA Drugs@FDA exact brand-name and generic-name query for sobetirome returned no matching application on 9 October 2026. This supports the US-scoped statement that no FDA-approved sobetirome product was located.

Participants / model
FDA application database, not a clinical population
Treatment
Exact substance-name search
Follow-up
Query run on 9 October 2026
Study design
Database query
Funding
not stated in the source

A US-scoped search result. It is not a statement about approvals in other countries.

Read the original source
2008 review by the originating investigator: designed for liver TR-beta selectivity

Animal study

Scanlan TS. Heart Fail Rev. 2010;15(2):177-82. PMID 19002578.

Sobetirome, also known as GC-1 and QRX-431, is a selective thyromimetic: a synthetic analog of thyroid hormone with tissue-specific thyroid hormone actions. It selectively binds to and activates thyroid hormone receptor beta over receptor alpha, and that receptor selectivity led to the hypothesis that it would lower cholesterol through activation of liver TR-beta without stimulating cardiac function through TR-alpha activation in the heart. The tissue-selective properties were demonstrated in numerous animal models, which led to clinical development as a cholesterol-lowering agent.

Participants / model
Animal models described in the review
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Review by the originating investigator
Funding
not stated in the source

A design rationale and summary of animal work, not a primary human report.

Read the original source

What did the animal studies find on cholesterol and metabolic rate?

In cholesterol-fed rats, GC-1 lowered cholesterol about 30 times more potently than it induced tachycardia and showed about 10-fold selectivity for metabolic rate over tachycardia. In cynomolgus monkeys it lowered cholesterol and lipoprotein(a) with no tachycardia.

The design rationale was that receptor selectivity would lower cholesterol through liver TR-beta without stimulating the heart through TR-alpha, and the 2008 review states the tissue-selective properties were demonstrated in numerous animal models.

In cholesterol-fed rats treated for 7 days, GC-1 reduced cholesterol with an ED50 of 190 nmol/kg per day, approximately 30 times more potently than it induced tachycardia (ED15 of 5451 nmol/kg per day), while T3 showed no potency difference between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold selectivity for increasing metabolic rate (ED5 of 477 nmol/kg per day) relative to tachycardia, where T3 again showed no selectivity.

In cynomolgus monkeys treated for 7 days, significant cholesterol lowering and lipoprotein(a) reduction were seen for both T3 and GC-1, while no tachycardia was observed for GC-1, unlike T3. T3 and GC-1 each caused a significant reduction of approximately 4% in body weight over those 7 days. The abstract does not state the route.

2008 review by the originating investigator: designed for liver TR-beta selectivity

Animal study

Scanlan TS. Heart Fail Rev. 2010;15(2):177-82. PMID 19002578.

Sobetirome, also known as GC-1 and QRX-431, is a selective thyromimetic: a synthetic analog of thyroid hormone with tissue-specific thyroid hormone actions. It selectively binds to and activates thyroid hormone receptor beta over receptor alpha, and that receptor selectivity led to the hypothesis that it would lower cholesterol through activation of liver TR-beta without stimulating cardiac function through TR-alpha activation in the heart. The tissue-selective properties were demonstrated in numerous animal models, which led to clinical development as a cholesterol-lowering agent.

Participants / model
Animal models described in the review
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Review by the originating investigator
Funding
not stated in the source

A design rationale and summary of animal work, not a primary human report.

Read the original source
Rats and monkeys, 7 days: cholesterol lowered about 30 times more potently than tachycardia was induced

Animal study

Grover GJ et al. Endocrinology. 2004;145(4):1656-61. PMID 14701670.

In cholesterol-fed rats treated for 7 days, GC-1 reduced cholesterol with an ED50 of 190 nmol/kg per day, approximately 30 times more potently than it induced tachycardia (ED15 of 5451 nmol/kg per day), while T3 showed no potency difference between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold selectivity for increasing metabolic rate (ED5 of 477 nmol/kg per day) relative to tachycardia, where T3 again showed no selectivity. In cynomolgus monkeys treated for 7 days, significant cholesterol lowering and lipoprotein(a) reduction were seen for both T3 and GC-1, while no tachycardia was observed for GC-1, unlike T3. T3 and GC-1 each caused a significant reduction of approximately 4% in body weight in the monkeys over those 7 days.

Participants / model
Cholesterol-fed rats and cynomolgus monkeys
Treatment
GC-1 and T3, 7 days; route not stated in the abstract
Follow-up
7 days
Study design
Original animal study
Funding
not stated in the source

The strongest preclinical evidence and it includes a primate. The abstract does not state the route.

Read the original source

What did the animal studies find on fat, muscle and exercise?

In a 6-week rat study, GC-1 reduced carcass fat by 15 to 23% against 14 to 74% for T3, while sparing skeletal muscle. In hypothyroid rats it restored swimming tolerance to normal, which is restoration of a deficit, not enhancement.

Adult female rats received 6 weeks of T3 by daily injection at 3 or 6 micrograms per 100 g body weight, or GC-1 at equimolar doses. All animals gained 17 to 25 g, not materially affected by either treatment. Only T3 selectively increased food intake, by 50 to 70%, and oxygen consumption was significantly and equally increased by T3 and GC-1, by 50 to 70%. By DEXA, control animals gained about 80% of fat mass, while T3-treated animals lost 70 to 90% and GC-1-treated animals lost approximately 20%. Direct carcass analysis showed T3 promoted a 14 to 74% decrease in fat content but GC-1 only a 15 to 23% reduction. Lean mass gain by DEXA and carcass protein content were not affected by either, and individual skeletal muscle mass was negatively affected by T3 but only barely by GC-1.

On fat loss, GC-1 was substantially weaker than T3 in this experiment, and what it preserved was muscle.

In rats made hypothyroid with methimazole sodium and perchlorate, six groups of eight animals underwent a swimming exercise tolerance test with a load attached to the tail after 8 weeks. Hypothyroidism significantly reduced exercise tolerance, and GC-1 at the 1x dose or physiological T4 restored it to normal. High-dose T4 decreased exercise tolerance, while 10x GC-1 did not impair it. Higher doses of T4 significantly increased cardiomyocyte diameter and induced soleus atrophy, whereas neither physiological T4 nor GC-1 at either dose changed cardiomyocyte diameter or relative soleus weight. This is restoration of a deficit in hypothyroid animals, not enhancement in healthy ones.

6-week rat study: carcass fat down 15 to 23% on GC-1 versus 14 to 74% on T3, muscle spared

Animal study

Villicev CM et al. J Endocrinol. 2007;193(1):21-9. PMID 17400799.

Adult female rats received 6 weeks of T3 by daily injection at 3 or 6 micrograms per 100 g body weight, or GC-1 at equimolar doses. All animals gained weight, 17 to 25 g, in a way not materially affected by either treatment. Only T3 selectively increased food intake, by 50 to 70%. Oxygen consumption was significantly and equally increased by T3 and GC-1, by 50 to 70%. By DEXA, control animals gained about 80% of fat mass, while T3-treated animals lost 70 to 90% and GC-1-treated animals lost approximately 20%. Direct carcass analysis showed T3 promoted a 14 to 74% decrease in fat content but GC-1 only a 15 to 23% reduction. Lean mass gain by DEXA and carcass protein content were not affected by either. Individual skeletal muscle mass was negatively affected by T3 but only barely by GC-1.

Participants / model
Adult female rats
Treatment
Daily injected T3 at 3 or 6 micrograms per 100 g body weight, or equimolar GC-1
Follow-up
6 weeks
Study design
Original animal study
Funding
not stated in the source

On fat loss, GC-1 was substantially weaker than T3 in this experiment; what it preserved was muscle.

Read the original source
Hypothyroid rats, 8 weeks: GC-1 restored swimming tolerance to normal without heart or soleus changes

Animal study

Gonçalves A et al. Arch Endocrinol Metab. 2015;59(2):141-7. PMID 25993677.

Hypothyroidism was induced with methimazole sodium and perchlorate. Six groups of eight animals were studied: control, untreated hypothyroid, hypothyroid treated with physiological T4 or 10 times that dose, and hypothyroid treated with equimolar GC-1 or 10 times that dose. After 8 weeks each animal underwent a swimming exercise tolerance test with a load attached to the tail. Hypothyroidism significantly reduced exercise tolerance, and GC-1 at the 1x dose or physiological T4 restored it to normal. High-dose T4 decreased exercise tolerance, while 10x GC-1 did not impair it. Higher doses of T4 significantly increased cardiomyocyte diameter and induced soleus atrophy, whereas neither physiological T4 nor GC-1 at either dose changed cardiomyocyte diameter or relative soleus weight.

Participants / model
48 rats in six groups of 8, with drug-induced hypothyroidism
Treatment
Physiological and 10x T4, or equimolar and 10x GC-1; route not stated in the abstract
Follow-up
8 weeks
Study design
Original animal study
Funding
not stated in the source

This is restoration of a deficit in hypothyroid animals, not enhancement in healthy ones.

Read the original source

What is known about sobetirome in people?

Two reviews state that sobetirome completed phase 1 trials, but no primary report was found, and both registered studies were withdrawn with no participants. No dose, duration, participant count, LDL figure or adverse event table is available.

A 2016 review states that sobetirome binds selectively to TR-beta1 over TR-alpha1, preferentially accumulates in liver, and progressed through preclinical animal studies and phase I human clinical trials, which the review describes as having excellent results and no obvious harmful side effects. The same review states it is unlikely to progress in further human clinical trials in the near future. It supplies no participant count, no dose, no duration and no lipid or body-weight number from any human study.

A 2020 review lists GC-1 (sobetirome) among four TR-beta-selective compounds that have been used in clinical trials, along with eprotirome (KB-2115), MB07344/VK2809 and resmetirom (MGL-3196), and states that each was able to reduce LDL cholesterol.

A ClinicalTrials.gov query on 9 October 2026 returned two sobetirome studies: NCT01787578, a phase 1 safety and pharmacodynamic study in X-linked adrenoleukodystrophy, and NCT03196765, a phase 1/2 study of NV1205 in pediatric male subjects with adrenoleukodystrophy. Both are recorded as withdrawn with 0 participants enrolled, and no registered study tests sobetirome for dyslipidemia, body composition, weight loss or metabolic rate.

A PubMed search on 9 October 2026 for sobetirome restricted to the humans MeSH term returned 55 records. Every record that refers to the phase 1 program is a review, and no primary report of a human trial was located. The statement that sobetirome completed phase 1 rests on two reviews asserting it.

2016 review: phase I reported as excellent, further human trials unlikely, no human numbers given

Human study

Lammel Lindemann J et al. Expert Opin Ther Targets. 2016;20(2):145-9. PMID 26565124.

A 2016 review states that sobetirome binds selectively to TR-beta1 over TR-alpha1 and preferentially accumulates in liver, and that it progressed through preclinical animal studies and phase I human clinical trials, which the review describes as having excellent results and no obvious harmful side effects. The same review states it is unlikely to progress in further human clinical trials in the near future, that the emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant, and that fears of thyrotoxic effects in the heart and the emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, have reduced enthusiasm for the strategy. The authors suggest sobetirome may have applications in orphan indications and short-term controlled weight loss. That suggestion is the authors' argument for future work, not a result. The review supplies no participant count, no dose, no duration and no lipid or body-weight number from any human study.

Participants / model
Human phase 1 participants described only in summary; dogs for the cartilage observation with a different compound
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Narrative review; no primary human data
Funding
not stated in the source

A narrative review. The phase 1 statement is the authors' assertion with no numbers behind it on this record.

Read the original source
2020 review: four TR-beta compounds lowered LDL; eprotirome phase 3 stopped the class

Human study

Zucchi R. Thyroid. 2020;30(8):1099-1105. PMID 32098589.

A 2020 review states that four TR-beta-selective compounds have been used in clinical trials: GC-1 (sobetirome), KB-2115 (eprotirome), MB07344/VK2809 and MGL-3196 (resmetirom). Each of these compounds was able to reduce low-density lipoprotein cholesterol, but a phase 3 trial with eprotirome was interrupted because of a significant increase in liver enzymes and the contemporary report of cartilage side effects in animals, and as a consequence the other projects were terminated as well. The review adds that TR-beta agonists later regained interest for nonalcoholic fatty liver disease, with trials started for MGL-3196 and VK2809, and that sobetirome turned out to be effective in experimental models of demyelinating disease.

Participants / model
Clinical trial programs for four compounds; animals for the cartilage observation
Treatment
Oral TR-beta-selective agonists
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

Class-level development history. The liver-enzyme and cartilage findings belong to eprotirome, not sobetirome.

Read the original source
Registry, 9 October 2026: two sobetirome studies, both withdrawn with 0 participants

Trial registry record

ClinicalTrials.gov query for sobetirome run on 9 October 2026; records NCT01787578 and NCT03196765.

A ClinicalTrials.gov query on 9 October 2026 returned two sobetirome studies: NCT01787578, a phase 1 safety and pharmacodynamic study in X-linked adrenoleukodystrophy, and NCT03196765, a phase 1/2 study of NV1205 in pediatric male subjects with adrenoleukodystrophy. Both are recorded as withdrawn with 0 participants enrolled. No registered study of sobetirome for dyslipidemia, body composition, weight loss or metabolic rate was located, and neither registered study enrolled anyone.

Participants / model
Records returned, not a population; 0 participants enrolled in either study
Treatment
Not applicable
Follow-up
Query run on 9 October 2026
Study design
Registry query
Funding
not stated in the source

The link opens the first record, NCT01787578.

Read the original source
PubMed search, 9 October 2026: 55 records, no primary human trial report

PubMed search record

PubMed search run on 9 October 2026: sobetirome AND humans[mh]. 55 records returned.

The search returned 55 records. Every record that refers to the phase 1 program is a review; the remainder are mouse, rat, cell, chemistry and prodrug studies, plus records matching the GC-1 cell line. No primary report of a sobetirome human trial was located, with no participant count, no dose, no duration, no LDL cholesterol figure, no metabolic rate figure and no adverse event table available from any source reviewed. The statement that sobetirome completed phase 1 rests entirely on two reviews asserting it.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Do the lipid, metabolic rate and fat loss claims hold up, especially for steroid users?

Lipid management and metabolic rate enhancement are supported in animals, and lipid effects in people are asserted by review only. Fat loss was weaker than T3's in rats, and no study examined sobetirome in steroid users.

Sellers describe sobetirome for lipid management, metabolic rate enhancement and fat loss, offered particularly to anabolic-androgenic steroid users with badly disrupted lipid panels.

The claim is three claims and they score differently. Lipid management is well supported in animals and asserted for people by review only. Metabolic rate enhancement is supported in rats at roughly 10-fold selectivity over tachycardia. Fat loss is the weakest: in the 6-week rat study GC-1 reduced carcass fat by 15 to 23% against 14 to 74% for T3, and body weight gain was not materially affected.

A PubMed search on 9 October 2026 for sobetirome with anabolic steroid, testosterone, bodybuilder, athlete or doping terms returned 3 records: two mouse reproductive-toxicology studies of chlormequat chloride and chlorocholine chloride that match on the GC-1 spermatogonial cell line rather than the compound, and the hypothyroid rat exercise-tolerance study. A broader search returned 35 records, all reproductive-toxicology or cell-biology studies matching the cell line. No study has examined sobetirome in anabolic-androgenic steroid users, in people with steroid-induced dyslipidemia, or alongside any androgen, and none has measured its effect on the HDL suppression that defines that lipid picture.

The supplier text also does not mention that, in mice, sobetirome at or above 10 micrograms per kg per day for 29 days depleted circulating T4 and T3 with normal TSH.

PubMed search, 9 October 2026: 3 records, none in steroid users

PubMed search record

PubMed search run on 9 October 2026: sobetirome AND ("anabolic steroid" OR testosterone OR bodybuilder OR athlete OR doping). 3 records returned. A broader search for sobetirome, GC-1 or thyromimetic with anabolic steroid, anabolic-androgenic, testosterone, bodybuilder or androgen terms returned 35 records.

The search returned 3 records: two mouse reproductive-toxicology studies of chlormequat chloride and chlorocholine chloride that match on the GC-1 spermatogonial cell line rather than the compound, and the hypothyroid rat exercise-tolerance study. A broader search for sobetirome, GC-1 or thyromimetic with anabolic steroid, anabolic-androgenic, testosterone, bodybuilder or androgen terms returned 35 records, all of which are reproductive-toxicology or cell-biology studies matching the GC-1 cell line. In the records reviewed, no study has examined sobetirome in anabolic-androgenic steroid users, in people with steroid-induced dyslipidemia, or alongside any androgen, and no study has measured its effect on the HDL suppression that defines that lipid picture.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Rats and monkeys, 7 days: cholesterol lowered about 30 times more potently than tachycardia was induced

Animal study

Grover GJ et al. Endocrinology. 2004;145(4):1656-61. PMID 14701670.

In cholesterol-fed rats treated for 7 days, GC-1 reduced cholesterol with an ED50 of 190 nmol/kg per day, approximately 30 times more potently than it induced tachycardia (ED15 of 5451 nmol/kg per day), while T3 showed no potency difference between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold selectivity for increasing metabolic rate (ED5 of 477 nmol/kg per day) relative to tachycardia, where T3 again showed no selectivity. In cynomolgus monkeys treated for 7 days, significant cholesterol lowering and lipoprotein(a) reduction were seen for both T3 and GC-1, while no tachycardia was observed for GC-1, unlike T3. T3 and GC-1 each caused a significant reduction of approximately 4% in body weight in the monkeys over those 7 days.

Participants / model
Cholesterol-fed rats and cynomolgus monkeys
Treatment
GC-1 and T3, 7 days; route not stated in the abstract
Follow-up
7 days
Study design
Original animal study
Funding
not stated in the source

The strongest preclinical evidence and it includes a primate. The abstract does not state the route.

Read the original source
6-week rat study: carcass fat down 15 to 23% on GC-1 versus 14 to 74% on T3, muscle spared

Animal study

Villicev CM et al. J Endocrinol. 2007;193(1):21-9. PMID 17400799.

Adult female rats received 6 weeks of T3 by daily injection at 3 or 6 micrograms per 100 g body weight, or GC-1 at equimolar doses. All animals gained weight, 17 to 25 g, in a way not materially affected by either treatment. Only T3 selectively increased food intake, by 50 to 70%. Oxygen consumption was significantly and equally increased by T3 and GC-1, by 50 to 70%. By DEXA, control animals gained about 80% of fat mass, while T3-treated animals lost 70 to 90% and GC-1-treated animals lost approximately 20%. Direct carcass analysis showed T3 promoted a 14 to 74% decrease in fat content but GC-1 only a 15 to 23% reduction. Lean mass gain by DEXA and carcass protein content were not affected by either. Individual skeletal muscle mass was negatively affected by T3 but only barely by GC-1.

Participants / model
Adult female rats
Treatment
Daily injected T3 at 3 or 6 micrograms per 100 g body weight, or equimolar GC-1
Follow-up
6 weeks
Study design
Original animal study
Funding
not stated in the source

On fat loss, GC-1 was substantially weaker than T3 in this experiment; what it preserved was muscle.

Read the original source
2016 review: phase I reported as excellent, further human trials unlikely, no human numbers given

Human study

Lammel Lindemann J et al. Expert Opin Ther Targets. 2016;20(2):145-9. PMID 26565124.

A 2016 review states that sobetirome binds selectively to TR-beta1 over TR-alpha1 and preferentially accumulates in liver, and that it progressed through preclinical animal studies and phase I human clinical trials, which the review describes as having excellent results and no obvious harmful side effects. The same review states it is unlikely to progress in further human clinical trials in the near future, that the emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant, and that fears of thyrotoxic effects in the heart and the emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, have reduced enthusiasm for the strategy. The authors suggest sobetirome may have applications in orphan indications and short-term controlled weight loss. That suggestion is the authors' argument for future work, not a result. The review supplies no participant count, no dose, no duration and no lipid or body-weight number from any human study.

Participants / model
Human phase 1 participants described only in summary; dogs for the cartilage observation with a different compound
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Narrative review; no primary human data
Funding
not stated in the source

A narrative review. The phase 1 statement is the authors' assertion with no numbers behind it on this record.

Read the original source
Mice, 29 days: T4 and T3 depleted with normal TSH at 10 micrograms per kg per day or more

Animal study

Ferrara SJ et al. Endocrinology. 2018;159(7):2733-2740. PMID 29846550.

Male C57BL/6 mice were dosed with sobetirome and with Sob-AM2, a CNS-targeted prodrug. Both suppressed hypothalamic-pituitary-thyroid axis gene transcript levels in a manner correlating with their tissue distribution, peripheral for sobetirome and central for the prodrug. Dosing at concentrations at or above 10 micrograms per kg per day for 29 days induced a state similar to central hypothyroidism, characterized by depleted circulating T4 and T3 with normal TSH levels. Despite the systemic T4 and T3 depletion the mice did not show signs of hypothyroidism, which the authors suggest may result from the thyromimetic being present in the hormone-depleted background.

Participants / model
Male C57BL/6 mice
Treatment
Sobetirome and Sob-AM2, at or above 10 micrograms per kg per day; route not stated in the abstract
Follow-up
29 days
Study design
Original animal study
Funding
not stated in the source

Sob-AM2 is a distinct CNS-targeted prodrug, and its results are not merged with sobetirome's on this page.

Read the original source

How does sobetirome work, and what does the body do with it?

Sobetirome binds and activates thyroid hormone receptor beta over alpha and accumulates preferentially in liver. In mice, dosing at or above 10 micrograms per kg per day for 29 days depleted T4 and T3 with normal TSH, and no pharmacokinetic data are given for people.

Sobetirome selectively binds to and activates thyroid hormone receptor beta over receptor alpha, and the 2016 review states that it preferentially accumulates in liver. That receptor selectivity led to the hypothesis that it would lower cholesterol through liver TR-beta without stimulating cardiac function through TR-alpha.

In male C57BL/6 mice dosed with sobetirome and with Sob-AM2, a CNS-targeted prodrug, both suppressed hypothalamic-pituitary-thyroid axis gene transcripts in a manner correlating with their tissue distribution, peripheral for sobetirome and central for the prodrug. In the study, dosing at concentrations at or above 10 micrograms per kg per day for 29 days induced a state similar to central hypothyroidism, characterized by depleted circulating T4 and T3 with normal TSH. Despite the T4 and T3 depletion the mice did not show signs of hypothyroidism, which the authors suggest may result from the thyromimetic being present in the hormone-depleted background.

Sob-AM2 is a distinct prodrug, and its results are not merged with sobetirome's here. The sources reviewed give no half-life, Tmax, bioavailability or human dose for sobetirome.

2008 review by the originating investigator: designed for liver TR-beta selectivity

Animal study

Scanlan TS. Heart Fail Rev. 2010;15(2):177-82. PMID 19002578.

Sobetirome, also known as GC-1 and QRX-431, is a selective thyromimetic: a synthetic analog of thyroid hormone with tissue-specific thyroid hormone actions. It selectively binds to and activates thyroid hormone receptor beta over receptor alpha, and that receptor selectivity led to the hypothesis that it would lower cholesterol through activation of liver TR-beta without stimulating cardiac function through TR-alpha activation in the heart. The tissue-selective properties were demonstrated in numerous animal models, which led to clinical development as a cholesterol-lowering agent.

Participants / model
Animal models described in the review
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Review by the originating investigator
Funding
not stated in the source

A design rationale and summary of animal work, not a primary human report.

Read the original source
2016 review: phase I reported as excellent, further human trials unlikely, no human numbers given

Human study

Lammel Lindemann J et al. Expert Opin Ther Targets. 2016;20(2):145-9. PMID 26565124.

A 2016 review states that sobetirome binds selectively to TR-beta1 over TR-alpha1 and preferentially accumulates in liver, and that it progressed through preclinical animal studies and phase I human clinical trials, which the review describes as having excellent results and no obvious harmful side effects. The same review states it is unlikely to progress in further human clinical trials in the near future, that the emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant, and that fears of thyrotoxic effects in the heart and the emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, have reduced enthusiasm for the strategy. The authors suggest sobetirome may have applications in orphan indications and short-term controlled weight loss. That suggestion is the authors' argument for future work, not a result. The review supplies no participant count, no dose, no duration and no lipid or body-weight number from any human study.

Participants / model
Human phase 1 participants described only in summary; dogs for the cartilage observation with a different compound
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Narrative review; no primary human data
Funding
not stated in the source

A narrative review. The phase 1 statement is the authors' assertion with no numbers behind it on this record.

Read the original source
Mice, 29 days: T4 and T3 depleted with normal TSH at 10 micrograms per kg per day or more

Animal study

Ferrara SJ et al. Endocrinology. 2018;159(7):2733-2740. PMID 29846550.

Male C57BL/6 mice were dosed with sobetirome and with Sob-AM2, a CNS-targeted prodrug. Both suppressed hypothalamic-pituitary-thyroid axis gene transcript levels in a manner correlating with their tissue distribution, peripheral for sobetirome and central for the prodrug. Dosing at concentrations at or above 10 micrograms per kg per day for 29 days induced a state similar to central hypothyroidism, characterized by depleted circulating T4 and T3 with normal TSH levels. Despite the systemic T4 and T3 depletion the mice did not show signs of hypothyroidism, which the authors suggest may result from the thyromimetic being present in the hormone-depleted background.

Participants / model
Male C57BL/6 mice
Treatment
Sobetirome and Sob-AM2, at or above 10 micrograms per kg per day; route not stated in the abstract
Follow-up
29 days
Study design
Original animal study
Funding
not stated in the source

Sob-AM2 is a distinct CNS-targeted prodrug, and its results are not merged with sobetirome's on this page.

Read the original source

What risks do the animal studies and class reports point to?

The risks come from animals and from related compounds, not from a human safety dataset. In rats GC-1 cut liver fat by 75% but caused fasting hyperglycemia and hyperinsulinemia, and in mice it depleted T4 and T3 with normal TSH. Eprotirome's liver enzyme and cartilage findings are not sobetirome's, but they ended the class.

In high-fat-fed male Sprague Dawley rats given GC-1 for 10 days, GC-1 reduced hepatic triglyceride content by 75%, but the rats developed fasting hyperglycemia and hyperinsulinemia, attributable to increased endogenous glucose production and diminished hepatic insulin sensitivity. GC-1 also increased white adipose tissue lipolysis, and the resulting glycerol flux may have contributed to the increased glucose production. The authors conclude that future TR-beta agonists must consider potential adverse effects on insulin sensitivity.

In mice, dosing at or above 10 micrograms per kg per day for 29 days depleted circulating T4 and T3 with normal TSH, a pattern the authors described as similar to central hypothyroidism.

A phase 3 trial of eprotirome (KB-2115), a similar but not identical compound, was interrupted because of a significant increase in liver enzymes and a contemporary report of cartilage side effects in animals. The 2016 review describes cartilage defects in dogs after long-term eprotirome and fears of thyrotoxic effects in the heart, and states these reduced enthusiasm for the strategy. Those liver-enzyme and cartilage findings belong to eprotirome and are not sobetirome findings, but they ended sobetirome's development: the other thyromimetic projects were terminated as a consequence.

No adverse event table from any human study of sobetirome is available in the sources reviewed.

High-fat-fed rats, 10 days: liver fat down 75% on GC-1 but fasting hyperglycemia and hyperinsulinemia

Animal study

Vatner DF et al. Am J Physiol Endocrinol Metab. 2013;305(1):E89-100. PMID 23651850.

Two TR-beta agonists, GC-1 and KB-2115, were given to high-fat-fed male Sprague Dawley rats for 10 days. GC-1 reduced hepatic triglyceride content by 75%, but the rats developed fasting hyperglycemia and hyperinsulinemia, attributable to increased endogenous glucose production and diminished hepatic insulin sensitivity. GC-1 also increased white adipose tissue lipolysis, and the resulting glycerol flux may have contributed to the increased glucose production. KB-2115, more liver-specific, also prevented hepatic steatosis without those effects, but diminished insulin-stimulated peripheral glucose disposal through reduced skeletal muscle glucose uptake and lower GLUT4 protein. The authors conclude both compounds potently treat hepatic steatosis but each worsens insulin action by a distinct mechanism, and that development of future TR-beta agonists must consider potential adverse effects on insulin sensitivity.

Participants / model
High-fat-fed male Sprague Dawley rats
Treatment
GC-1 and KB-2115, 10 days; route and dose not stated in the abstract
Follow-up
10 days
Study design
Original animal study
Funding
not stated in the source

KB-2115 is eprotirome, a different compound; its results are not sobetirome's.

Read the original source
Mice, 29 days: T4 and T3 depleted with normal TSH at 10 micrograms per kg per day or more

Animal study

Ferrara SJ et al. Endocrinology. 2018;159(7):2733-2740. PMID 29846550.

Male C57BL/6 mice were dosed with sobetirome and with Sob-AM2, a CNS-targeted prodrug. Both suppressed hypothalamic-pituitary-thyroid axis gene transcript levels in a manner correlating with their tissue distribution, peripheral for sobetirome and central for the prodrug. Dosing at concentrations at or above 10 micrograms per kg per day for 29 days induced a state similar to central hypothyroidism, characterized by depleted circulating T4 and T3 with normal TSH levels. Despite the systemic T4 and T3 depletion the mice did not show signs of hypothyroidism, which the authors suggest may result from the thyromimetic being present in the hormone-depleted background.

Participants / model
Male C57BL/6 mice
Treatment
Sobetirome and Sob-AM2, at or above 10 micrograms per kg per day; route not stated in the abstract
Follow-up
29 days
Study design
Original animal study
Funding
not stated in the source

Sob-AM2 is a distinct CNS-targeted prodrug, and its results are not merged with sobetirome's on this page.

Read the original source
2020 review: four TR-beta compounds lowered LDL; eprotirome phase 3 stopped the class

Human study

Zucchi R. Thyroid. 2020;30(8):1099-1105. PMID 32098589.

A 2020 review states that four TR-beta-selective compounds have been used in clinical trials: GC-1 (sobetirome), KB-2115 (eprotirome), MB07344/VK2809 and MGL-3196 (resmetirom). Each of these compounds was able to reduce low-density lipoprotein cholesterol, but a phase 3 trial with eprotirome was interrupted because of a significant increase in liver enzymes and the contemporary report of cartilage side effects in animals, and as a consequence the other projects were terminated as well. The review adds that TR-beta agonists later regained interest for nonalcoholic fatty liver disease, with trials started for MGL-3196 and VK2809, and that sobetirome turned out to be effective in experimental models of demyelinating disease.

Participants / model
Clinical trial programs for four compounds; animals for the cartilage observation
Treatment
Oral TR-beta-selective agonists
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

Class-level development history. The liver-enzyme and cartilage findings belong to eprotirome, not sobetirome.

Read the original source
2016 review: phase I reported as excellent, further human trials unlikely, no human numbers given

Human study

Lammel Lindemann J et al. Expert Opin Ther Targets. 2016;20(2):145-9. PMID 26565124.

A 2016 review states that sobetirome binds selectively to TR-beta1 over TR-alpha1 and preferentially accumulates in liver, and that it progressed through preclinical animal studies and phase I human clinical trials, which the review describes as having excellent results and no obvious harmful side effects. The same review states it is unlikely to progress in further human clinical trials in the near future, that the emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant, and that fears of thyrotoxic effects in the heart and the emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, have reduced enthusiasm for the strategy. The authors suggest sobetirome may have applications in orphan indications and short-term controlled weight loss. That suggestion is the authors' argument for future work, not a result. The review supplies no participant count, no dose, no duration and no lipid or body-weight number from any human study.

Participants / model
Human phase 1 participants described only in summary; dogs for the cartilage observation with a different compound
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Narrative review; no primary human data
Funding
not stated in the source

A narrative review. The phase 1 statement is the authors' assertion with no numbers behind it on this record.

Read the original source

Why does sobetirome sit in C tier?

The animal mechanism is demonstrated and quantified, but the human side is empty: two reviews state phase 1 trials were completed, no primary report was found, and both registered studies were withdrawn with no participants. The steroid-user framing has no evidence behind it.

The mechanism is demonstrated and quantified: about 30-fold separation between cholesterol lowering and tachycardia in rats, cholesterol and lipoprotein(a) reduction without tachycardia in cynomolgus monkeys, and preserved skeletal muscle where T3 caused loss. That is stronger preclinical work than most compounds at this grade get.

What holds it at C is the human side. Two reviews state that phase 1 trials were completed with excellent results, and no primary report exists in the records reviewed, so there is no dose, duration, participant count, lipid figure or adverse event table to quote. Both registered sobetirome studies were withdrawn with 0 participants. Development ended on a related compound's phase 3 liver-enzyme signal and canine cartilage findings, not on sobetirome's own data.

On the supplier claim, lipid management is supported in animals, metabolic rate enhancement is supported in rats, and fat loss is the weakest. Not one record in the searches run on 9 October 2026 examines sobetirome in steroid users, in steroid-induced dyslipidemia or alongside any androgen.

Rats and monkeys, 7 days: cholesterol lowered about 30 times more potently than tachycardia was induced

Animal study

Grover GJ et al. Endocrinology. 2004;145(4):1656-61. PMID 14701670.

In cholesterol-fed rats treated for 7 days, GC-1 reduced cholesterol with an ED50 of 190 nmol/kg per day, approximately 30 times more potently than it induced tachycardia (ED15 of 5451 nmol/kg per day), while T3 showed no potency difference between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold selectivity for increasing metabolic rate (ED5 of 477 nmol/kg per day) relative to tachycardia, where T3 again showed no selectivity. In cynomolgus monkeys treated for 7 days, significant cholesterol lowering and lipoprotein(a) reduction were seen for both T3 and GC-1, while no tachycardia was observed for GC-1, unlike T3. T3 and GC-1 each caused a significant reduction of approximately 4% in body weight in the monkeys over those 7 days.

Participants / model
Cholesterol-fed rats and cynomolgus monkeys
Treatment
GC-1 and T3, 7 days; route not stated in the abstract
Follow-up
7 days
Study design
Original animal study
Funding
not stated in the source

The strongest preclinical evidence and it includes a primate. The abstract does not state the route.

Read the original source
2016 review: phase I reported as excellent, further human trials unlikely, no human numbers given

Human study

Lammel Lindemann J et al. Expert Opin Ther Targets. 2016;20(2):145-9. PMID 26565124.

A 2016 review states that sobetirome binds selectively to TR-beta1 over TR-alpha1 and preferentially accumulates in liver, and that it progressed through preclinical animal studies and phase I human clinical trials, which the review describes as having excellent results and no obvious harmful side effects. The same review states it is unlikely to progress in further human clinical trials in the near future, that the emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant, and that fears of thyrotoxic effects in the heart and the emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, have reduced enthusiasm for the strategy. The authors suggest sobetirome may have applications in orphan indications and short-term controlled weight loss. That suggestion is the authors' argument for future work, not a result. The review supplies no participant count, no dose, no duration and no lipid or body-weight number from any human study.

Participants / model
Human phase 1 participants described only in summary; dogs for the cartilage observation with a different compound
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Narrative review; no primary human data
Funding
not stated in the source

A narrative review. The phase 1 statement is the authors' assertion with no numbers behind it on this record.

Read the original source
2020 review: four TR-beta compounds lowered LDL; eprotirome phase 3 stopped the class

Human study

Zucchi R. Thyroid. 2020;30(8):1099-1105. PMID 32098589.

A 2020 review states that four TR-beta-selective compounds have been used in clinical trials: GC-1 (sobetirome), KB-2115 (eprotirome), MB07344/VK2809 and MGL-3196 (resmetirom). Each of these compounds was able to reduce low-density lipoprotein cholesterol, but a phase 3 trial with eprotirome was interrupted because of a significant increase in liver enzymes and the contemporary report of cartilage side effects in animals, and as a consequence the other projects were terminated as well. The review adds that TR-beta agonists later regained interest for nonalcoholic fatty liver disease, with trials started for MGL-3196 and VK2809, and that sobetirome turned out to be effective in experimental models of demyelinating disease.

Participants / model
Clinical trial programs for four compounds; animals for the cartilage observation
Treatment
Oral TR-beta-selective agonists
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

Class-level development history. The liver-enzyme and cartilage findings belong to eprotirome, not sobetirome.

Read the original source
Registry, 9 October 2026: two sobetirome studies, both withdrawn with 0 participants

Trial registry record

ClinicalTrials.gov query for sobetirome run on 9 October 2026; records NCT01787578 and NCT03196765.

A ClinicalTrials.gov query on 9 October 2026 returned two sobetirome studies: NCT01787578, a phase 1 safety and pharmacodynamic study in X-linked adrenoleukodystrophy, and NCT03196765, a phase 1/2 study of NV1205 in pediatric male subjects with adrenoleukodystrophy. Both are recorded as withdrawn with 0 participants enrolled. No registered study of sobetirome for dyslipidemia, body composition, weight loss or metabolic rate was located, and neither registered study enrolled anyone.

Participants / model
Records returned, not a population; 0 participants enrolled in either study
Treatment
Not applicable
Follow-up
Query run on 9 October 2026
Study design
Registry query
Funding
not stated in the source

The link opens the first record, NCT01787578.

Read the original source
PubMed search, 9 October 2026: 55 records, no primary human trial report

PubMed search record

PubMed search run on 9 October 2026: sobetirome AND humans[mh]. 55 records returned.

The search returned 55 records. Every record that refers to the phase 1 program is a review; the remainder are mouse, rat, cell, chemistry and prodrug studies, plus records matching the GC-1 cell line. No primary report of a sobetirome human trial was located, with no participant count, no dose, no duration, no LDL cholesterol figure, no metabolic rate figure and no adverse event table available from any source reviewed. The statement that sobetirome completed phase 1 rests entirely on two reviews asserting it.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
PubMed search, 9 October 2026: 3 records, none in steroid users

PubMed search record

PubMed search run on 9 October 2026: sobetirome AND ("anabolic steroid" OR testosterone OR bodybuilder OR athlete OR doping). 3 records returned. A broader search for sobetirome, GC-1 or thyromimetic with anabolic steroid, anabolic-androgenic, testosterone, bodybuilder or androgen terms returned 35 records.

The search returned 3 records: two mouse reproductive-toxicology studies of chlormequat chloride and chlorocholine chloride that match on the GC-1 spermatogonial cell line rather than the compound, and the hypothyroid rat exercise-tolerance study. A broader search for sobetirome, GC-1 or thyromimetic with anabolic steroid, anabolic-androgenic, testosterone, bodybuilder or androgen terms returned 35 records, all of which are reproductive-toxicology or cell-biology studies matching the GC-1 cell line. In the records reviewed, no study has examined sobetirome in anabolic-androgenic steroid users, in people with steroid-induced dyslipidemia, or alongside any androgen, and no study has measured its effect on the HDL suppression that defines that lipid picture.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

PubChem CID 9862248: C20H24O4, 328.4 g/mol; GC-1 naming collision

Chemical identity record

National Library of Medicine. PubChem compound record CID 9862248 (sobetirome, GC-1, QRX-431).

Sobetirome: PubChem CID 9862248, C20H24O4, 328.4 g/mol, CAS 211110-63-3. Listed synonyms include GC-1 and QRX-431. GC-1 is also the established name of a widely used mouse spermatogonial cell line, and a PubMed search on the bare string GC-1 returns mostly that cell line rather than this compound. Any citation attributed to 'GC-1' has to be read for which GC-1 it means.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, no approved formulation
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source
2008 review by the originating investigator: designed for liver TR-beta selectivity

Animal study

Scanlan TS. Heart Fail Rev. 2010;15(2):177-82. PMID 19002578.

Sobetirome, also known as GC-1 and QRX-431, is a selective thyromimetic: a synthetic analog of thyroid hormone with tissue-specific thyroid hormone actions. It selectively binds to and activates thyroid hormone receptor beta over receptor alpha, and that receptor selectivity led to the hypothesis that it would lower cholesterol through activation of liver TR-beta without stimulating cardiac function through TR-alpha activation in the heart. The tissue-selective properties were demonstrated in numerous animal models, which led to clinical development as a cholesterol-lowering agent.

Participants / model
Animal models described in the review
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Review by the originating investigator
Funding
not stated in the source

A design rationale and summary of animal work, not a primary human report.

Read the original source
2016 review: phase I reported as excellent, further human trials unlikely, no human numbers given

Human study

Lammel Lindemann J et al. Expert Opin Ther Targets. 2016;20(2):145-9. PMID 26565124.

A 2016 review states that sobetirome binds selectively to TR-beta1 over TR-alpha1 and preferentially accumulates in liver, and that it progressed through preclinical animal studies and phase I human clinical trials, which the review describes as having excellent results and no obvious harmful side effects. The same review states it is unlikely to progress in further human clinical trials in the near future, that the emergence of alternative cholesterol-lowering therapeutics may render selective thyromimetics redundant, and that fears of thyrotoxic effects in the heart and the emergence of cartilage defects in dogs after long-term use of eprotirome, a similar though not identical compound, have reduced enthusiasm for the strategy. The authors suggest sobetirome may have applications in orphan indications and short-term controlled weight loss. That suggestion is the authors' argument for future work, not a result. The review supplies no participant count, no dose, no duration and no lipid or body-weight number from any human study.

Participants / model
Human phase 1 participants described only in summary; dogs for the cartilage observation with a different compound
Treatment
Not specified in the abstract
Follow-up
not stated in the source
Study design
Narrative review; no primary human data
Funding
not stated in the source

A narrative review. The phase 1 statement is the authors' assertion with no numbers behind it on this record.

Read the original source
2020 review: four TR-beta compounds lowered LDL; eprotirome phase 3 stopped the class

Human study

Zucchi R. Thyroid. 2020;30(8):1099-1105. PMID 32098589.

A 2020 review states that four TR-beta-selective compounds have been used in clinical trials: GC-1 (sobetirome), KB-2115 (eprotirome), MB07344/VK2809 and MGL-3196 (resmetirom). Each of these compounds was able to reduce low-density lipoprotein cholesterol, but a phase 3 trial with eprotirome was interrupted because of a significant increase in liver enzymes and the contemporary report of cartilage side effects in animals, and as a consequence the other projects were terminated as well. The review adds that TR-beta agonists later regained interest for nonalcoholic fatty liver disease, with trials started for MGL-3196 and VK2809, and that sobetirome turned out to be effective in experimental models of demyelinating disease.

Participants / model
Clinical trial programs for four compounds; animals for the cartilage observation
Treatment
Oral TR-beta-selective agonists
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

Class-level development history. The liver-enzyme and cartilage findings belong to eprotirome, not sobetirome.

Read the original source
Rats and monkeys, 7 days: cholesterol lowered about 30 times more potently than tachycardia was induced

Animal study

Grover GJ et al. Endocrinology. 2004;145(4):1656-61. PMID 14701670.

In cholesterol-fed rats treated for 7 days, GC-1 reduced cholesterol with an ED50 of 190 nmol/kg per day, approximately 30 times more potently than it induced tachycardia (ED15 of 5451 nmol/kg per day), while T3 showed no potency difference between cholesterol lowering and tachycardia. GC-1 showed approximately 10-fold selectivity for increasing metabolic rate (ED5 of 477 nmol/kg per day) relative to tachycardia, where T3 again showed no selectivity. In cynomolgus monkeys treated for 7 days, significant cholesterol lowering and lipoprotein(a) reduction were seen for both T3 and GC-1, while no tachycardia was observed for GC-1, unlike T3. T3 and GC-1 each caused a significant reduction of approximately 4% in body weight in the monkeys over those 7 days.

Participants / model
Cholesterol-fed rats and cynomolgus monkeys
Treatment
GC-1 and T3, 7 days; route not stated in the abstract
Follow-up
7 days
Study design
Original animal study
Funding
not stated in the source

The strongest preclinical evidence and it includes a primate. The abstract does not state the route.

Read the original source
6-week rat study: carcass fat down 15 to 23% on GC-1 versus 14 to 74% on T3, muscle spared

Animal study

Villicev CM et al. J Endocrinol. 2007;193(1):21-9. PMID 17400799.

Adult female rats received 6 weeks of T3 by daily injection at 3 or 6 micrograms per 100 g body weight, or GC-1 at equimolar doses. All animals gained weight, 17 to 25 g, in a way not materially affected by either treatment. Only T3 selectively increased food intake, by 50 to 70%. Oxygen consumption was significantly and equally increased by T3 and GC-1, by 50 to 70%. By DEXA, control animals gained about 80% of fat mass, while T3-treated animals lost 70 to 90% and GC-1-treated animals lost approximately 20%. Direct carcass analysis showed T3 promoted a 14 to 74% decrease in fat content but GC-1 only a 15 to 23% reduction. Lean mass gain by DEXA and carcass protein content were not affected by either. Individual skeletal muscle mass was negatively affected by T3 but only barely by GC-1.

Participants / model
Adult female rats
Treatment
Daily injected T3 at 3 or 6 micrograms per 100 g body weight, or equimolar GC-1
Follow-up
6 weeks
Study design
Original animal study
Funding
not stated in the source

On fat loss, GC-1 was substantially weaker than T3 in this experiment; what it preserved was muscle.

Read the original source
Mice, 29 days: T4 and T3 depleted with normal TSH at 10 micrograms per kg per day or more

Animal study

Ferrara SJ et al. Endocrinology. 2018;159(7):2733-2740. PMID 29846550.

Male C57BL/6 mice were dosed with sobetirome and with Sob-AM2, a CNS-targeted prodrug. Both suppressed hypothalamic-pituitary-thyroid axis gene transcript levels in a manner correlating with their tissue distribution, peripheral for sobetirome and central for the prodrug. Dosing at concentrations at or above 10 micrograms per kg per day for 29 days induced a state similar to central hypothyroidism, characterized by depleted circulating T4 and T3 with normal TSH levels. Despite the systemic T4 and T3 depletion the mice did not show signs of hypothyroidism, which the authors suggest may result from the thyromimetic being present in the hormone-depleted background.

Participants / model
Male C57BL/6 mice
Treatment
Sobetirome and Sob-AM2, at or above 10 micrograms per kg per day; route not stated in the abstract
Follow-up
29 days
Study design
Original animal study
Funding
not stated in the source

Sob-AM2 is a distinct CNS-targeted prodrug, and its results are not merged with sobetirome's on this page.

Read the original source
High-fat-fed rats, 10 days: liver fat down 75% on GC-1 but fasting hyperglycemia and hyperinsulinemia

Animal study

Vatner DF et al. Am J Physiol Endocrinol Metab. 2013;305(1):E89-100. PMID 23651850.

Two TR-beta agonists, GC-1 and KB-2115, were given to high-fat-fed male Sprague Dawley rats for 10 days. GC-1 reduced hepatic triglyceride content by 75%, but the rats developed fasting hyperglycemia and hyperinsulinemia, attributable to increased endogenous glucose production and diminished hepatic insulin sensitivity. GC-1 also increased white adipose tissue lipolysis, and the resulting glycerol flux may have contributed to the increased glucose production. KB-2115, more liver-specific, also prevented hepatic steatosis without those effects, but diminished insulin-stimulated peripheral glucose disposal through reduced skeletal muscle glucose uptake and lower GLUT4 protein. The authors conclude both compounds potently treat hepatic steatosis but each worsens insulin action by a distinct mechanism, and that development of future TR-beta agonists must consider potential adverse effects on insulin sensitivity.

Participants / model
High-fat-fed male Sprague Dawley rats
Treatment
GC-1 and KB-2115, 10 days; route and dose not stated in the abstract
Follow-up
10 days
Study design
Original animal study
Funding
not stated in the source

KB-2115 is eprotirome, a different compound; its results are not sobetirome's.

Read the original source
Hypothyroid rats, 8 weeks: GC-1 restored swimming tolerance to normal without heart or soleus changes

Animal study

Gonçalves A et al. Arch Endocrinol Metab. 2015;59(2):141-7. PMID 25993677.

Hypothyroidism was induced with methimazole sodium and perchlorate. Six groups of eight animals were studied: control, untreated hypothyroid, hypothyroid treated with physiological T4 or 10 times that dose, and hypothyroid treated with equimolar GC-1 or 10 times that dose. After 8 weeks each animal underwent a swimming exercise tolerance test with a load attached to the tail. Hypothyroidism significantly reduced exercise tolerance, and GC-1 at the 1x dose or physiological T4 restored it to normal. High-dose T4 decreased exercise tolerance, while 10x GC-1 did not impair it. Higher doses of T4 significantly increased cardiomyocyte diameter and induced soleus atrophy, whereas neither physiological T4 nor GC-1 at either dose changed cardiomyocyte diameter or relative soleus weight.

Participants / model
48 rats in six groups of 8, with drug-induced hypothyroidism
Treatment
Physiological and 10x T4, or equimolar and 10x GC-1; route not stated in the abstract
Follow-up
8 weeks
Study design
Original animal study
Funding
not stated in the source

This is restoration of a deficit in hypothyroid animals, not enhancement in healthy ones.

Read the original source
Registry, 9 October 2026: two sobetirome studies, both withdrawn with 0 participants

Trial registry record

ClinicalTrials.gov query for sobetirome run on 9 October 2026; records NCT01787578 and NCT03196765.

A ClinicalTrials.gov query on 9 October 2026 returned two sobetirome studies: NCT01787578, a phase 1 safety and pharmacodynamic study in X-linked adrenoleukodystrophy, and NCT03196765, a phase 1/2 study of NV1205 in pediatric male subjects with adrenoleukodystrophy. Both are recorded as withdrawn with 0 participants enrolled. No registered study of sobetirome for dyslipidemia, body composition, weight loss or metabolic rate was located, and neither registered study enrolled anyone.

Participants / model
Records returned, not a population; 0 participants enrolled in either study
Treatment
Not applicable
Follow-up
Query run on 9 October 2026
Study design
Registry query
Funding
not stated in the source

The link opens the first record, NCT01787578.

Read the original source

Why is Sobetirome in C tier?

C fits a compound whose animal mechanism is demonstrated and quantified: about 30-fold separation between cholesterol lowering and tachycardia in rats, cholesterol and lipoprotein(a) reduction without tachycardia in monkeys, and preserved skeletal muscle where T3 caused loss. The human side is empty: two reviews state phase 1 trials were completed, no primary report was found, and both registered studies were withdrawn with no participants. Development ended on a related compound's phase 3 liver-enzyme signal, not on sobetirome's own data, and nothing in the records tests the steroid-user claim.