CMS-121 (CMS121)

updated

CMS-121 (CMS121) is a research compound that its developers describe as a fisetin derivative, sold for neuroprotection, cognitive preservation with age and less neuroinflammation. Its efficacy work is cell culture and mouse models, nearly all from the group that holds the patent, and no human efficacy study exists: a PubMed query on 10 October 2026 found no record of CMS121 given to a patient. A completed Phase 1 trial in 99 healthy volunteers is registered with no posted results, and a 2025 preprint that is not peer reviewed reports tolerability and pharmacokinetics in healthy adults.

Fatty acid synthase and acetyl-CoA carboxylase 1 inhibitor (developers' account)

  • CMS121 is PubChem CID 135741221, C20H19NO3, molecular weight 321.4, a quinoline carrying a catechol ring; fisetin is a different molecule, a flavonol.
  • In SAMP8 fast-aging mice, CMS121 reduced cognitive decline and brain aging markers, and in 16 female SAMP8 mice fed CMS121 the hearing threshold at 12 kHz was 39.8 versus 56.5.
  • In wild-type mice fed a CMS121 diet for 6 months, weight gain fell 40% and resting metabolic rate was higher, and in db/db mice body weight fell 5%.
  • NCT05318040 is a completed Phase 1 trial in 99 healthy volunteers aged 19 to 85, sponsored by Virogenics, Inc., with no results posted as of 10 October 2026.
  • A 2025 medRxiv preprint that is not peer reviewed reports single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days in healthy adults as generally well tolerated.
  • A PubMed query on 10 October 2026 found no record of CMS121 given to a patient, a cognitive outcome in a person or a randomized efficacy trial.

What is CMS-121, and what is its regulatory status?

CMS-121 is a research compound, PubChem CID 135741221, that its developers describe as a fisetin derivative; its structure is a quinoline with a catechol ring, not the flavonol fisetin. It has no FDA label, and ClinicalTrials.gov lists one completed Phase 1 trial in healthy volunteers with no posted results.

CMS121, also written CMS-121, is PubChem CID 135741221, C20H19NO3, 321.4 g/mol, with CAS 1353224-53-9 among the synonyms and the IUPAC name 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol. That name describes a quinoline carrying a catechol ring.

Fisetin is a flavonol (PubChem CID 5281614, C15H10O6, 286.24 g/mol, 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one), so 'fisetin derivative' is the authors' account of the medicinal chemistry lineage and not a statement that CMS121 keeps the flavonol skeleton. A 2024 Huntington's disease paper says CMS121 was selected from 160 synthetic fisetin derivatives. The Salk Institute holds the patent (US9744164, from the authors' conflict statements), and the name CMS-121 is also used for the tool compound in unrelated cell papers on ACC1 and FASN. CMS121 is not a substitute for fisetin as a supplement: the structures differ and no study compares them.

A product sold as CMS-121 cannot be tied to the studied material by the name, and no public record ties any vendor material to it. On 10 October 2026 DailyMed returned no label for CMS121 and an openFDA Drugs@FDA query returned no match. ClinicalTrials.gov lists one study, NCT05318040, a completed Phase 1 trial in healthy volunteers described in the Phase 1 section below, with no posted results. Status outside the United States is not covered here.

PubChem: CMS121 identity, and fisetin for comparison

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 135741221, 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol (CMS121).

CMS121, also written CMS-121, is PubChem CID 135741221, C20H19NO3, 321.4 g/mol, CAS 1353224-53-9 (listed among the synonyms), IUPAC name 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol, with UNII BW9P9F8JEY among the synonyms. That name describes a quinoline carrying a catechol ring. Fisetin is a flavonol (PubChem CID 5281614, C15H10O6, 286.24 g/mol, 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one), so 'fisetin derivative' is the authors' account of the medicinal chemistry lineage and not a statement that CMS121 keeps the flavonol skeleton. The 2024 Huntington's disease paper says CMS121 was selected from 160 synthetic fisetin derivatives and cites the 2012 chemistry paper. The Salk Institute holds the patent (US9744164, from the authors' conflict statements), and the compound is also the tool compound 'CMS-121' in unrelated cell papers on ACC1 and FASN.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, free form
Follow-up
Not applicable
Study design
Chemical database record
Funding
not stated in the source

Identity record only. A product sold as CMS-121 cannot be tied to the studied material by the name, and no public record ties any vendor material to it. CMS121 is not a fisetin supplement substitute: the structures differ and no study compares them.

Read the original source
Label searches, 10 October 2026: no label, no match

Regulatory record

U.S. Food and Drug Administration (DailyMed label search; openFDA Drugs@FDA query). Searches for CMS121, run 10 October 2026.

DailyMed returned no label for CMS121, and the openFDA Drugs@FDA query returned no match. ClinicalTrials.gov lists one study, NCT05318040, a completed Phase 1 trial in healthy volunteers.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated label and application search
Funding
not stated in the source

An absence finding as of 10 October 2026. It covers United States label and application records only.

Read the original source
Registered Phase 1 in 99 healthy volunteers, aged 19 to 85, no posted results

Trial registry record

ClinicalTrials.gov. NCT05318040. Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion; United States.

A Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. It is complete: start 2022-05-01, primary completion 2022-12-17, 99 participants enrolled (actual), ages 19 to 85, last record update 2023-02-16, and no results posted on the registry as of 2026-10-10. Design: randomized, double-blind, placebo-controlled single ascending doses in young adults, multiple ascending doses in young adults, multiple doses in elderly volunteers, and an open-label two-way crossover food-effect part. The primary outcome is treatment-emergent adverse events. Capsules were given orally. The condition field says Alzheimer Disease, but the volunteers were healthy.

Participants / model
Healthy volunteers aged 19 to 85; 99 enrolled (actual)
Treatment
Oral CMS121 capsules, single and multiple ascending doses, with a food-effect crossover part
Follow-up
Start 2022-05-01; primary completion 2022-12-17
Study design
Phase 1, randomized, double-blind, placebo-controlled ascending-dose parts plus an open-label food-effect crossover
Funding
Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion (registry record)

No results posted as of 2026-10-10. The trial tests safety and pharmacokinetics in healthy people, not efficacy, even though the condition field says Alzheimer Disease. Any later publication or results posting would need to be read before this page is updated.

Read the original source

What did the mouse and cell studies find?

In transgenic Alzheimer's mice CMS121 alleviated cognitive loss and reduced brain inflammation and lipid peroxidation, in SAMP8 fast-aging mice it reduced cognitive decline, aging markers and hearing loss, and in two Huntington's disease models it slowed motor dysfunction and increased median life span. All of it is mouse and cell work, nearly all from the group that discovered it, and no human efficacy study exists.

In transgenic Alzheimer's disease mice CMS121 alleviated cognitive loss, modulated lipid metabolism, and reduced inflammation and lipid peroxidation in the brain, and FASN was identified as a target. The abstract does not name the mouse line, the dose, the route or effect sizes. This is the source for the less-neuroinflammation wording, and it is one mouse study from the discovering group.

In senescence-accelerated SAMP8 mice, CMS121 and J147 reduced cognitive decline and metabolic and transcriptional markers of aging in the brain, preserved mitochondrial homeostasis through acetyl-CoA metabolism and increased H3K9 acetylation. When mice were fed J147 or CMS121 in the last quarter of their lifespan, both improved physiological markers for brain and kidney function, and drug treatment restored a more youthful protein profile in each organ. The route in these studies was diet according to the 2021 abstract; doses and cognitive test details are not in the abstracts.

A collaboration with a hearing laboratory fed CMS121 in the diet to 16 female SAMP8 mice and reported lower hearing thresholds at 12 kHz (39.8 versus 56.5, p = 0.044) and 16 kHz (43.8 versus 64.8, p = 0.040) at 13 weeks of age, and more preserved inner hair cell ribbon synapses (18.4 versus 15.7 per cell, p = 0.014). The authors include Currais, Maher and Schubert. SAMP8 is an accelerated-aging model, not normal aging in mice and not a result in people.

In R6/2 and YAC128 Huntington's disease mice, CMS121 slowed motor dysfunction and increased median life span, partially attenuating disease, and the authors state CMS121 could provide some benefits for HD patients. That is the authors' view and not a result in people.

Transgenic Alzheimer's mice: less cognitive loss, inflammation and lipid peroxidation

Animal study

Ates G et al. Redox Biol. 2020;36:101648. PMID 32863221.

In transgenic Alzheimer's disease mice CMS121 alleviated cognitive loss, modulated lipid metabolism, and reduced inflammation and lipid peroxidation in the brain, and FASN was identified as a target. The abstract does not name the mouse line, the dose, the route or effect sizes.

Participants / model
Transgenic Alzheimer's disease mice
Treatment
CMS121; dose and route not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the source for the less-neuroinflammation wording, and it is one mouse study from the discovering group.

Read the original source
SAMP8 fast-aging mice: cognition, aging markers, brain and kidney proteins, hearing

Animal study

Currais A et al. Elife. 2019;8. PMID 31742554.

In senescence-accelerated SAMP8 mice, CMS121 and J147 reduced cognitive decline and metabolic and transcriptional markers of aging in the brain, preserved mitochondrial homeostasis through acetyl-CoA metabolism, and increased H3K9 acetylation. When mice were fed J147 or CMS121 in the last quarter of their lifespan, both improved physiological markers for brain and kidney function, and drug treatment restored a more youthful protein profile in each organ (PMID 33550278). A collaboration with a hearing laboratory, in 16 female SAMP8 mice fed CMS121 in the diet, reported lower hearing thresholds at 12 kHz (39.8 versus 56.5, p = 0.044) and 16 kHz (43.8 versus 64.8, p = 0.040) at 13 weeks of age, and more preserved inner hair cell ribbon synapses (18.4 versus 15.7 per cell, p = 0.014) (PMID 37097512; the authors include Currais, Maher and Schubert).

Participants / model
SAMP8 mice, including 16 female SAMP8 mice in the hearing study
Treatment
CMS121 fed in the diet (stated in PMID 33550278 and PMID 37097512); doses and cognitive test details not in the abstracts
Follow-up
Last quarter of lifespan in the 2021 study; to 13 weeks of age in the hearing study
Study design
Original preclinical studies
Funding
not stated in the source

SAMP8 is an accelerated-aging model, not normal aging in mice or any result in people.

Read the original source
Huntington's disease, db/db and wild-type mice: motor function, survival, glucose, body weight

Animal study

Dafre AL et al. Aging (Albany NY). 2024;16(6):4980-4999. PMID 38517358.

In wild-type mice fed a CMS121 diet for 6 months, weight gain fell 40% and glucose and lipid indexes improved, with a higher resting metabolic rate. In R6/2 and YAC128 Huntington's disease mice, CMS121 slowed motor dysfunction and increased median life span, 'partially' attenuating disease, and the authors state CMS121 could provide some benefits for HD patients (PMID 37864765). In db/db mice fed CMS121 for 6 months, body weight fell 5% and glucose tolerance, HbA1c, insulin, triglycerides, liver inflammation markers and urine markers of kidney damage improved (PMID 37047807).

Participants / model
R6/2 and YAC128 Huntington's disease mice; db/db mice; wild-type mice
Treatment
CMS121 fed in the diet; 6 months in the db/db and wild-type studies; doses not stated in the abstracts
Follow-up
6 months in the db/db and wild-type studies; not stated for the Huntington's disease study
Study design
Original preclinical studies
Funding
not stated in the source

Reduced weight gain in non-obese animals is an effect that belongs with the results, because CMS121 is described as a brain-aging compound.

Read the original source

Did CMS-121 change body weight in mice?

Yes. In db/db mice fed CMS121 for 6 months body weight fell 5%, and in wild-type mice fed a CMS121 diet for 6 months weight gain fell 40% with a higher resting metabolic rate. Reduced weight gain in non-obese animals is a result to know about for a compound sold for brain aging.

In db/db mice fed CMS121 for 6 months, body weight fell 5% and glucose tolerance, HbA1c, insulin, triglycerides, liver inflammation markers and urine markers of kidney damage improved. In wild-type mice fed a CMS121 diet for 6 months, weight gain fell 40% and glucose and lipid indexes improved, with a higher resting metabolic rate.

Reduced weight gain in non-obese animals belongs with the results, because CMS121 is described as a brain-aging compound. These are mouse findings from dietary dosing, and the abstracts give no doses.

Huntington's disease, db/db and wild-type mice: motor function, survival, glucose, body weight

Animal study

Dafre AL et al. Aging (Albany NY). 2024;16(6):4980-4999. PMID 38517358.

In wild-type mice fed a CMS121 diet for 6 months, weight gain fell 40% and glucose and lipid indexes improved, with a higher resting metabolic rate. In R6/2 and YAC128 Huntington's disease mice, CMS121 slowed motor dysfunction and increased median life span, 'partially' attenuating disease, and the authors state CMS121 could provide some benefits for HD patients (PMID 37864765). In db/db mice fed CMS121 for 6 months, body weight fell 5% and glucose tolerance, HbA1c, insulin, triglycerides, liver inflammation markers and urine markers of kidney damage improved (PMID 37047807).

Participants / model
R6/2 and YAC128 Huntington's disease mice; db/db mice; wild-type mice
Treatment
CMS121 fed in the diet; 6 months in the db/db and wild-type studies; doses not stated in the abstracts
Follow-up
6 months in the db/db and wild-type studies; not stated for the Huntington's disease study
Study design
Original preclinical studies
Funding
not stated in the source

Reduced weight gain in non-obese animals is an effect that belongs with the results, because CMS121 is described as a brain-aging compound.

Read the original source

How does CMS-121 act on fatty acid metabolism?

The group that discovered CMS121 reports that it inhibits fatty acid synthase (FASN) and, in a 2019 paper, acetyl-CoA carboxylase 1 (ACC1), raising acetyl-CoA and histone H3K9 acetylation and reducing lipid peroxidation. It was found by adding protection against oxytosis and ferroptosis to a cell-based screen, and the mechanism is reported by the group that holds the patent.

A 2020 mouse paper identifies fatty acid synthase (FASN) as a molecular target of CMS121 and says it modulates lipid metabolism and reduces lipid peroxidation. A 2019 paper reports that CMS121 and J147, which it describes as distinct in structure, increased acetyl-CoA in cell culture and mice through inhibition of acetyl-CoA carboxylase 1 (ACC1), with neuroprotection and increased histone H3K9 acetylation in SAMP8 mice.

In SAMP8 mice CMS121 preserved mitochondrial homeostasis through acetyl-CoA metabolism. A 2024 review by the discovering group says CMS121 was found by adding protection against oxytosis and ferroptosis to a cell-based screen for Alzheimer's drug candidates, and the 2012 chemistry paper reports that fisetin itself has a relatively high EC50, low lipophilicity and poor bioavailability, which led to the derivative screen.

All of this mechanism work comes from the group that owns the patent, and none of it has been tested in people.

Origin and target: fisetin screen, FASN and ACC1 inhibition, acetyl-CoA, ferroptosis screen

Cell study

Chiruta C et al. J Med Chem. 2012;55(1):378-89. PMID 22192055.

The 2012 paper reports that fisetin has a relatively high EC50 in cell assays, low lipophilicity, high topological polar surface area and poor bioavailability, and describes a screen that found fisetin derivatives with significantly enhanced activity in an in vitro neuroprotection model; the abstract does not name CMS121. A 2020 mouse paper identifies fatty acid synthase (FASN) as a molecular target of CMS121 and says it modulates lipid metabolism and reduces lipid peroxidation. A 2019 paper reports that CMS121 and J147, which it describes as distinct in structure, increased acetyl-CoA in cell culture and mice through inhibition of acetyl-CoA carboxylase 1 (ACC1), with neuroprotection and increased histone H3K9 acetylation in SAMP8 mice. The 2024 review by the discovering group says CMS121 was found by adding protection against oxytosis and ferroptosis to a cell-based screen for Alzheimer's drug candidates (PMID 39422940).

Participants / model
Cell lines; mice
Treatment
Cell culture; the in vivo route is not stated in the abstracts
Follow-up
not stated in the source
Study design
Original preclinical studies; review
Funding
not stated in the source

The mechanism is reported by the group that owns the patent. The 2012 abstract does not name CMS121.

Read the original source
Transgenic Alzheimer's mice: less cognitive loss, inflammation and lipid peroxidation

Animal study

Ates G et al. Redox Biol. 2020;36:101648. PMID 32863221.

In transgenic Alzheimer's disease mice CMS121 alleviated cognitive loss, modulated lipid metabolism, and reduced inflammation and lipid peroxidation in the brain, and FASN was identified as a target. The abstract does not name the mouse line, the dose, the route or effect sizes.

Participants / model
Transgenic Alzheimer's disease mice
Treatment
CMS121; dose and route not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the source for the less-neuroinflammation wording, and it is one mouse study from the discovering group.

Read the original source
SAMP8 fast-aging mice: cognition, aging markers, brain and kidney proteins, hearing

Animal study

Currais A et al. Elife. 2019;8. PMID 31742554.

In senescence-accelerated SAMP8 mice, CMS121 and J147 reduced cognitive decline and metabolic and transcriptional markers of aging in the brain, preserved mitochondrial homeostasis through acetyl-CoA metabolism, and increased H3K9 acetylation. When mice were fed J147 or CMS121 in the last quarter of their lifespan, both improved physiological markers for brain and kidney function, and drug treatment restored a more youthful protein profile in each organ (PMID 33550278). A collaboration with a hearing laboratory, in 16 female SAMP8 mice fed CMS121 in the diet, reported lower hearing thresholds at 12 kHz (39.8 versus 56.5, p = 0.044) and 16 kHz (43.8 versus 64.8, p = 0.040) at 13 weeks of age, and more preserved inner hair cell ribbon synapses (18.4 versus 15.7 per cell, p = 0.014) (PMID 37097512; the authors include Currais, Maher and Schubert).

Participants / model
SAMP8 mice, including 16 female SAMP8 mice in the hearing study
Treatment
CMS121 fed in the diet (stated in PMID 33550278 and PMID 37097512); doses and cognitive test details not in the abstracts
Follow-up
Last quarter of lifespan in the 2021 study; to 13 weeks of age in the hearing study
Study design
Original preclinical studies
Funding
not stated in the source

SAMP8 is an accelerated-aging model, not normal aging in mice or any result in people.

Read the original source

What did the Phase 1 registration and the preprint report?

ClinicalTrials.gov lists one completed Phase 1 trial of CMS121 in 99 healthy volunteers aged 19 to 85 with no results posted as of 10 October 2026, and a 2025 medRxiv preprint that is not peer reviewed reports single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days as generally well tolerated. Both address tolerability and pharmacokinetics in healthy people, not benefit.

The registry record NCT05318040 is a Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers, sponsored by Virogenics, Inc. with the National Institute on Aging and Celerion as collaborators, in the United States. It is complete: start 2022-05-01, primary completion 2022-12-17, 99 participants enrolled, ages 19 to 85, last record update 2023-02-16, and no results posted as of 10 October 2026. The design is randomized, double-blind and placebo-controlled for single ascending doses in young adults, multiple ascending doses in young adults and multiple doses in elderly volunteers, plus an open-label two-way crossover food-effect part. The primary outcome is treatment-emergent adverse events. The condition field says Alzheimer Disease, but the volunteers were healthy, so the trial tests safety and pharmacokinetics, not efficacy.

A 2025 medRxiv preprint by Maher, Christopher, Evans and Raschke reports single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days in healthy adults, generally well tolerated with the majority of treatment-emergent adverse events mild. Pharmacokinetics of CMS121 and its metabolites rose in a dose-proportional or slightly greater than dose-proportional way, the CMS121-C2 metabolite contributed most to molar-equivalent CMS121 in plasma, and metabolites had minimal urinary excretion. Elderly subjects had higher exposures and longer terminal half-lives, and exposure was about 50% higher in the fed state.

The preprint's abstract states no adverse event counts, no QT or other cardiodynamic result and no sample size, and it is not peer reviewed in the records reviewed. Its abstract does not name the registry number, so whether it reports NCT05318040 is not stated. A 2024 review abstract says it covers the toxicology testing that led to the IND approval and gives no results.

Registered Phase 1 in 99 healthy volunteers, aged 19 to 85, no posted results

Trial registry record

ClinicalTrials.gov. NCT05318040. Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion; United States.

A Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. It is complete: start 2022-05-01, primary completion 2022-12-17, 99 participants enrolled (actual), ages 19 to 85, last record update 2023-02-16, and no results posted on the registry as of 2026-10-10. Design: randomized, double-blind, placebo-controlled single ascending doses in young adults, multiple ascending doses in young adults, multiple doses in elderly volunteers, and an open-label two-way crossover food-effect part. The primary outcome is treatment-emergent adverse events. Capsules were given orally. The condition field says Alzheimer Disease, but the volunteers were healthy.

Participants / model
Healthy volunteers aged 19 to 85; 99 enrolled (actual)
Treatment
Oral CMS121 capsules, single and multiple ascending doses, with a food-effect crossover part
Follow-up
Start 2022-05-01; primary completion 2022-12-17
Study design
Phase 1, randomized, double-blind, placebo-controlled ascending-dose parts plus an open-label food-effect crossover
Funding
Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion (registry record)

No results posted as of 2026-10-10. The trial tests safety and pharmacokinetics in healthy people, not efficacy, even though the condition field says Alzheimer Disease. Any later publication or results posting would need to be read before this page is updated.

Read the original source
2025 preprint, not peer reviewed: single doses to 1800 mg, 7-day doses to 900 mg per day, healthy adults

Human study

Maher P et al. medRxiv. 2025. PMID 40093210.

A 2025 medRxiv preprint by Maher, Christopher, Evans and Raschke reports single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days in healthy adults, 'generally well tolerated' with the majority of treatment-emergent adverse events mild. Pharmacokinetics of CMS121 and its metabolites rose in a dose-proportional or slightly greater than dose-proportional way, with the CMS121-C2 metabolite contributing most to molar-equivalent CMS121 in plasma, and minimal urinary excretion of metabolites. Elderly subjects had higher exposures and longer terminal half-lives, and exposure was about 50% higher in the fed state. The abstract states no adverse event counts, no QT or other cardiodynamic result and no sample size. The 2024 review abstract says it covers the toxicology testing that led to the IND approval and gives no results (PMID 39422940).

Participants / model
Healthy adults, including elderly subjects
Treatment
Oral CMS121, single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days
Follow-up
Single dose and 7 days of repeat dosing
Study design
Phase 1 healthy-volunteer study reported as a preprint; not peer reviewed in the records reviewed
Funding
not stated in the source

A preprint and not peer reviewed. The abstract does not name the registry number, so whether it reports NCT05318040 is not stated. No safety sentence beyond 'generally well tolerated' with mostly mild events is made here.

Read the original source

Is CMS-121 a fisetin derivative that protects the aging brain?

Partly, and only in cells and mice. 'A fisetin derivative' is accurate as a description of the design lineage and not of the structure. Neuroprotection and less neuroinflammation are supported in cell and transgenic mouse work, and cognitive preservation with age only in SAMP8 and transgenic mice. No study tests any of these in people, and a registered Phase 1 trial and a preprint address tolerability, not benefit.

Sellers describe a fisetin derivative that protects neurons, preserves cognition with age and lowers neuroinflammation. The fisetin lineage is the developers' account of how the molecule was designed, and its structure is a quinoline with a catechol ring. Neuroprotection and less neuroinflammation are supported in cell work and in one transgenic Alzheimer's mouse study. Cognitive preservation with age is supported only in SAMP8 accelerated-aging mice and transgenic mice.

No study tests these effects in people. A PubMed query on 10 October 2026 for the CMS-121, CMS121 and CMS 121 spellings returned 13 records, and abstracts were read for all 13. Eight carry human or trial terms, and of those only the Phase 1 preprint reports people; none reports CMS121 given to a patient, a cognitive outcome in a person or a randomized efficacy trial. Three records use CMS121 as a FASN or ACC1 inhibitor in cell work on HSV-1 infection, fatty liver cells and endothelial cells, and a fourth, a 2026 BCG trained-immunity paper, does not name CMS121 in its abstract, so none of these supports the supplier claim.

ClinicalTrials.gov queries for CMS121, CMS-121 and VG-CMS121 each returned only NCT05318040, and queries for CMS121 fisetin derivative and fisetin derivative Alzheimer returned none. No controlled efficacy trial in people exists in the records reviewed.

Transgenic Alzheimer's mice: less cognitive loss, inflammation and lipid peroxidation

Animal study

Ates G et al. Redox Biol. 2020;36:101648. PMID 32863221.

In transgenic Alzheimer's disease mice CMS121 alleviated cognitive loss, modulated lipid metabolism, and reduced inflammation and lipid peroxidation in the brain, and FASN was identified as a target. The abstract does not name the mouse line, the dose, the route or effect sizes.

Participants / model
Transgenic Alzheimer's disease mice
Treatment
CMS121; dose and route not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the source for the less-neuroinflammation wording, and it is one mouse study from the discovering group.

Read the original source
SAMP8 fast-aging mice: cognition, aging markers, brain and kidney proteins, hearing

Animal study

Currais A et al. Elife. 2019;8. PMID 31742554.

In senescence-accelerated SAMP8 mice, CMS121 and J147 reduced cognitive decline and metabolic and transcriptional markers of aging in the brain, preserved mitochondrial homeostasis through acetyl-CoA metabolism, and increased H3K9 acetylation. When mice were fed J147 or CMS121 in the last quarter of their lifespan, both improved physiological markers for brain and kidney function, and drug treatment restored a more youthful protein profile in each organ (PMID 33550278). A collaboration with a hearing laboratory, in 16 female SAMP8 mice fed CMS121 in the diet, reported lower hearing thresholds at 12 kHz (39.8 versus 56.5, p = 0.044) and 16 kHz (43.8 versus 64.8, p = 0.040) at 13 weeks of age, and more preserved inner hair cell ribbon synapses (18.4 versus 15.7 per cell, p = 0.014) (PMID 37097512; the authors include Currais, Maher and Schubert).

Participants / model
SAMP8 mice, including 16 female SAMP8 mice in the hearing study
Treatment
CMS121 fed in the diet (stated in PMID 33550278 and PMID 37097512); doses and cognitive test details not in the abstracts
Follow-up
Last quarter of lifespan in the 2021 study; to 13 weeks of age in the hearing study
Study design
Original preclinical studies
Funding
not stated in the source

SAMP8 is an accelerated-aging model, not normal aging in mice or any result in people.

Read the original source
PubMed, 10 October 2026: 13 records, none gives CMS121 to a patient

PubMed search record

PubMed search run 10 October 2026: "CMS-121"[tiab] OR CMS121[tiab] OR "CMS 121"[tiab], with a follow-up screen of the records for human or trial terms (human, patients, volunteers, clinical, trial, randomized, phase 1 or 2).

The search returned 13 records, and abstracts were read for all 13. Eight carry human or trial terms; of those only the Phase 1 preprint reports people, and none reports CMS121 given to a patient, a cognitive outcome in a person, or a randomized efficacy trial. Three records use CMS121 or CMS-121 as a FASN or ACC1 inhibitor in cell work (HSV-1 infection, fatty liver cells, endothelial cells), and a fourth, a 2026 BCG trained-immunity paper (PMID 42642930), does not name CMS121 in its abstract; these are not evidence for the supplier claim. ClinicalTrials.gov queries for CMS121, 'CMS-121' and 'CMS121' OR 'CMS-121' OR 'VG-CMS121' each returned only NCT05318040, and queries for 'CMS121 fisetin derivative' and 'fisetin derivative Alzheimer' returned none.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature and registry search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source
PubChem: CMS121 identity, and fisetin for comparison

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 135741221, 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol (CMS121).

CMS121, also written CMS-121, is PubChem CID 135741221, C20H19NO3, 321.4 g/mol, CAS 1353224-53-9 (listed among the synonyms), IUPAC name 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol, with UNII BW9P9F8JEY among the synonyms. That name describes a quinoline carrying a catechol ring. Fisetin is a flavonol (PubChem CID 5281614, C15H10O6, 286.24 g/mol, 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one), so 'fisetin derivative' is the authors' account of the medicinal chemistry lineage and not a statement that CMS121 keeps the flavonol skeleton. The 2024 Huntington's disease paper says CMS121 was selected from 160 synthetic fisetin derivatives and cites the 2012 chemistry paper. The Salk Institute holds the patent (US9744164, from the authors' conflict statements), and the compound is also the tool compound 'CMS-121' in unrelated cell papers on ACC1 and FASN.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, free form
Follow-up
Not applicable
Study design
Chemical database record
Funding
not stated in the source

Identity record only. A product sold as CMS-121 cannot be tied to the studied material by the name, and no public record ties any vendor material to it. CMS121 is not a fisetin supplement substitute: the structures differ and no study compares them.

Read the original source

What is known about the safety of CMS-121?

The safety record in people is one completed Phase 1 trial with no posted results and a 2025 preprint that is not peer reviewed and calls doses up to 1800 mg single and 900 mg per day for 7 days generally well tolerated. Its abstract gives no adverse event counts, cardiac result or sample size. In mice CMS121 reduced weight gain even in non-obese animals, and the identity of vendor material is not established.

In people, the only information is the registered Phase 1 trial, which has no posted results, and the 2025 preprint, which says single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days in healthy adults were generally well tolerated with the majority of treatment-emergent adverse events mild. The abstract gives no adverse event counts or types, no QT or other cardiodynamic result and no sample size, and the preprint is not peer reviewed, so no safety statement beyond that is made here.

The preprint abstract reports exposure about 50% higher in the fed state and higher exposures and longer terminal half-lives in elderly subjects, with no half-life figure given. A 2024 review abstract refers to toxicology testing that led to the IND approval and gives no results.

In mice fed CMS121 for 6 months, body weight fell 5% in db/db mice and weight gain fell 40% in non-obese wild-type mice, a metabolic effect that is not part of a brain-aging description.

Product identity is a separate concern. A product sold as CMS-121 cannot be tied to the studied material by the name, and CMS121 is not interchangeable with fisetin.

Registered Phase 1 in 99 healthy volunteers, aged 19 to 85, no posted results

Trial registry record

ClinicalTrials.gov. NCT05318040. Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion; United States.

A Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. It is complete: start 2022-05-01, primary completion 2022-12-17, 99 participants enrolled (actual), ages 19 to 85, last record update 2023-02-16, and no results posted on the registry as of 2026-10-10. Design: randomized, double-blind, placebo-controlled single ascending doses in young adults, multiple ascending doses in young adults, multiple doses in elderly volunteers, and an open-label two-way crossover food-effect part. The primary outcome is treatment-emergent adverse events. Capsules were given orally. The condition field says Alzheimer Disease, but the volunteers were healthy.

Participants / model
Healthy volunteers aged 19 to 85; 99 enrolled (actual)
Treatment
Oral CMS121 capsules, single and multiple ascending doses, with a food-effect crossover part
Follow-up
Start 2022-05-01; primary completion 2022-12-17
Study design
Phase 1, randomized, double-blind, placebo-controlled ascending-dose parts plus an open-label food-effect crossover
Funding
Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion (registry record)

No results posted as of 2026-10-10. The trial tests safety and pharmacokinetics in healthy people, not efficacy, even though the condition field says Alzheimer Disease. Any later publication or results posting would need to be read before this page is updated.

Read the original source
2025 preprint, not peer reviewed: single doses to 1800 mg, 7-day doses to 900 mg per day, healthy adults

Human study

Maher P et al. medRxiv. 2025. PMID 40093210.

A 2025 medRxiv preprint by Maher, Christopher, Evans and Raschke reports single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days in healthy adults, 'generally well tolerated' with the majority of treatment-emergent adverse events mild. Pharmacokinetics of CMS121 and its metabolites rose in a dose-proportional or slightly greater than dose-proportional way, with the CMS121-C2 metabolite contributing most to molar-equivalent CMS121 in plasma, and minimal urinary excretion of metabolites. Elderly subjects had higher exposures and longer terminal half-lives, and exposure was about 50% higher in the fed state. The abstract states no adverse event counts, no QT or other cardiodynamic result and no sample size. The 2024 review abstract says it covers the toxicology testing that led to the IND approval and gives no results (PMID 39422940).

Participants / model
Healthy adults, including elderly subjects
Treatment
Oral CMS121, single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days
Follow-up
Single dose and 7 days of repeat dosing
Study design
Phase 1 healthy-volunteer study reported as a preprint; not peer reviewed in the records reviewed
Funding
not stated in the source

A preprint and not peer reviewed. The abstract does not name the registry number, so whether it reports NCT05318040 is not stated. No safety sentence beyond 'generally well tolerated' with mostly mild events is made here.

Read the original source
Huntington's disease, db/db and wild-type mice: motor function, survival, glucose, body weight

Animal study

Dafre AL et al. Aging (Albany NY). 2024;16(6):4980-4999. PMID 38517358.

In wild-type mice fed a CMS121 diet for 6 months, weight gain fell 40% and glucose and lipid indexes improved, with a higher resting metabolic rate. In R6/2 and YAC128 Huntington's disease mice, CMS121 slowed motor dysfunction and increased median life span, 'partially' attenuating disease, and the authors state CMS121 could provide some benefits for HD patients (PMID 37864765). In db/db mice fed CMS121 for 6 months, body weight fell 5% and glucose tolerance, HbA1c, insulin, triglycerides, liver inflammation markers and urine markers of kidney damage improved (PMID 37047807).

Participants / model
R6/2 and YAC128 Huntington's disease mice; db/db mice; wild-type mice
Treatment
CMS121 fed in the diet; 6 months in the db/db and wild-type studies; doses not stated in the abstracts
Follow-up
6 months in the db/db and wild-type studies; not stated for the Huntington's disease study
Study design
Original preclinical studies
Funding
not stated in the source

Reduced weight gain in non-obese animals is an effect that belongs with the results, because CMS121 is described as a brain-aging compound.

Read the original source
PubChem: CMS121 identity, and fisetin for comparison

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 135741221, 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol (CMS121).

CMS121, also written CMS-121, is PubChem CID 135741221, C20H19NO3, 321.4 g/mol, CAS 1353224-53-9 (listed among the synonyms), IUPAC name 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol, with UNII BW9P9F8JEY among the synonyms. That name describes a quinoline carrying a catechol ring. Fisetin is a flavonol (PubChem CID 5281614, C15H10O6, 286.24 g/mol, 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one), so 'fisetin derivative' is the authors' account of the medicinal chemistry lineage and not a statement that CMS121 keeps the flavonol skeleton. The 2024 Huntington's disease paper says CMS121 was selected from 160 synthetic fisetin derivatives and cites the 2012 chemistry paper. The Salk Institute holds the patent (US9744164, from the authors' conflict statements), and the compound is also the tool compound 'CMS-121' in unrelated cell papers on ACC1 and FASN.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, free form
Follow-up
Not applicable
Study design
Chemical database record
Funding
not stated in the source

Identity record only. A product sold as CMS-121 cannot be tied to the studied material by the name, and no public record ties any vendor material to it. CMS121 is not a fisetin supplement substitute: the structures differ and no study compares them.

Read the original source

Why does CMS-121 sit in C tier?

CMS-121 has a wider preclinical package than most research chemicals and a registered, completed Phase 1 trial, but efficacy is shown only in mice, almost all from the group that holds the patent, with no human efficacy data, no peer-reviewed human paper and no posted trial results.

The preclinical package is wide: several mouse models (transgenic Alzheimer's, SAMP8 aging, Huntington's disease, db/db and wild-type metabolism), a defined molecular target in FASN and ACC1, a registered and completed Phase 1 trial with 99 participants, and a preprint reporting tolerability up to 1800 mg as a single dose.

The data are thin where the supplier claim lives. Efficacy is shown only in mice, almost all of it from the group linked to the patent holder, the cognitive findings are in accelerated-aging and transgenic models, there are no human efficacy data, no peer-reviewed human paper and no posted trial results.

SAMP8 fast-aging mice: cognition, aging markers, brain and kidney proteins, hearing

Animal study

Currais A et al. Elife. 2019;8. PMID 31742554.

In senescence-accelerated SAMP8 mice, CMS121 and J147 reduced cognitive decline and metabolic and transcriptional markers of aging in the brain, preserved mitochondrial homeostasis through acetyl-CoA metabolism, and increased H3K9 acetylation. When mice were fed J147 or CMS121 in the last quarter of their lifespan, both improved physiological markers for brain and kidney function, and drug treatment restored a more youthful protein profile in each organ (PMID 33550278). A collaboration with a hearing laboratory, in 16 female SAMP8 mice fed CMS121 in the diet, reported lower hearing thresholds at 12 kHz (39.8 versus 56.5, p = 0.044) and 16 kHz (43.8 versus 64.8, p = 0.040) at 13 weeks of age, and more preserved inner hair cell ribbon synapses (18.4 versus 15.7 per cell, p = 0.014) (PMID 37097512; the authors include Currais, Maher and Schubert).

Participants / model
SAMP8 mice, including 16 female SAMP8 mice in the hearing study
Treatment
CMS121 fed in the diet (stated in PMID 33550278 and PMID 37097512); doses and cognitive test details not in the abstracts
Follow-up
Last quarter of lifespan in the 2021 study; to 13 weeks of age in the hearing study
Study design
Original preclinical studies
Funding
not stated in the source

SAMP8 is an accelerated-aging model, not normal aging in mice or any result in people.

Read the original source
Transgenic Alzheimer's mice: less cognitive loss, inflammation and lipid peroxidation

Animal study

Ates G et al. Redox Biol. 2020;36:101648. PMID 32863221.

In transgenic Alzheimer's disease mice CMS121 alleviated cognitive loss, modulated lipid metabolism, and reduced inflammation and lipid peroxidation in the brain, and FASN was identified as a target. The abstract does not name the mouse line, the dose, the route or effect sizes.

Participants / model
Transgenic Alzheimer's disease mice
Treatment
CMS121; dose and route not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the source for the less-neuroinflammation wording, and it is one mouse study from the discovering group.

Read the original source
Registered Phase 1 in 99 healthy volunteers, aged 19 to 85, no posted results

Trial registry record

ClinicalTrials.gov. NCT05318040. Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion; United States.

A Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. It is complete: start 2022-05-01, primary completion 2022-12-17, 99 participants enrolled (actual), ages 19 to 85, last record update 2023-02-16, and no results posted on the registry as of 2026-10-10. Design: randomized, double-blind, placebo-controlled single ascending doses in young adults, multiple ascending doses in young adults, multiple doses in elderly volunteers, and an open-label two-way crossover food-effect part. The primary outcome is treatment-emergent adverse events. Capsules were given orally. The condition field says Alzheimer Disease, but the volunteers were healthy.

Participants / model
Healthy volunteers aged 19 to 85; 99 enrolled (actual)
Treatment
Oral CMS121 capsules, single and multiple ascending doses, with a food-effect crossover part
Follow-up
Start 2022-05-01; primary completion 2022-12-17
Study design
Phase 1, randomized, double-blind, placebo-controlled ascending-dose parts plus an open-label food-effect crossover
Funding
Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion (registry record)

No results posted as of 2026-10-10. The trial tests safety and pharmacokinetics in healthy people, not efficacy, even though the condition field says Alzheimer Disease. Any later publication or results posting would need to be read before this page is updated.

Read the original source
2025 preprint, not peer reviewed: single doses to 1800 mg, 7-day doses to 900 mg per day, healthy adults

Human study

Maher P et al. medRxiv. 2025. PMID 40093210.

A 2025 medRxiv preprint by Maher, Christopher, Evans and Raschke reports single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days in healthy adults, 'generally well tolerated' with the majority of treatment-emergent adverse events mild. Pharmacokinetics of CMS121 and its metabolites rose in a dose-proportional or slightly greater than dose-proportional way, with the CMS121-C2 metabolite contributing most to molar-equivalent CMS121 in plasma, and minimal urinary excretion of metabolites. Elderly subjects had higher exposures and longer terminal half-lives, and exposure was about 50% higher in the fed state. The abstract states no adverse event counts, no QT or other cardiodynamic result and no sample size. The 2024 review abstract says it covers the toxicology testing that led to the IND approval and gives no results (PMID 39422940).

Participants / model
Healthy adults, including elderly subjects
Treatment
Oral CMS121, single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days
Follow-up
Single dose and 7 days of repeat dosing
Study design
Phase 1 healthy-volunteer study reported as a preprint; not peer reviewed in the records reviewed
Funding
not stated in the source

A preprint and not peer reviewed. The abstract does not name the registry number, so whether it reports NCT05318040 is not stated. No safety sentence beyond 'generally well tolerated' with mostly mild events is made here.

Read the original source
PubMed, 10 October 2026: 13 records, none gives CMS121 to a patient

PubMed search record

PubMed search run 10 October 2026: "CMS-121"[tiab] OR CMS121[tiab] OR "CMS 121"[tiab], with a follow-up screen of the records for human or trial terms (human, patients, volunteers, clinical, trial, randomized, phase 1 or 2).

The search returned 13 records, and abstracts were read for all 13. Eight carry human or trial terms; of those only the Phase 1 preprint reports people, and none reports CMS121 given to a patient, a cognitive outcome in a person, or a randomized efficacy trial. Three records use CMS121 or CMS-121 as a FASN or ACC1 inhibitor in cell work (HSV-1 infection, fatty liver cells, endothelial cells), and a fourth, a 2026 BCG trained-immunity paper (PMID 42642930), does not name CMS121 in its abstract; these are not evidence for the supplier claim. ClinicalTrials.gov queries for CMS121, 'CMS-121' and 'CMS121' OR 'CMS-121' OR 'VG-CMS121' each returned only NCT05318040, and queries for 'CMS121 fisetin derivative' and 'fisetin derivative Alzheimer' returned none.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature and registry search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source

Studies and sources

PubChem: CMS121 identity, and fisetin for comparison

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 135741221, 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol (CMS121).

CMS121, also written CMS-121, is PubChem CID 135741221, C20H19NO3, 321.4 g/mol, CAS 1353224-53-9 (listed among the synonyms), IUPAC name 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol, with UNII BW9P9F8JEY among the synonyms. That name describes a quinoline carrying a catechol ring. Fisetin is a flavonol (PubChem CID 5281614, C15H10O6, 286.24 g/mol, 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one), so 'fisetin derivative' is the authors' account of the medicinal chemistry lineage and not a statement that CMS121 keeps the flavonol skeleton. The 2024 Huntington's disease paper says CMS121 was selected from 160 synthetic fisetin derivatives and cites the 2012 chemistry paper. The Salk Institute holds the patent (US9744164, from the authors' conflict statements), and the compound is also the tool compound 'CMS-121' in unrelated cell papers on ACC1 and FASN.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule, free form
Follow-up
Not applicable
Study design
Chemical database record
Funding
not stated in the source

Identity record only. A product sold as CMS-121 cannot be tied to the studied material by the name, and no public record ties any vendor material to it. CMS121 is not a fisetin supplement substitute: the structures differ and no study compares them.

Read the original source
Origin and target: fisetin screen, FASN and ACC1 inhibition, acetyl-CoA, ferroptosis screen

Cell study

Chiruta C et al. J Med Chem. 2012;55(1):378-89. PMID 22192055.

The 2012 paper reports that fisetin has a relatively high EC50 in cell assays, low lipophilicity, high topological polar surface area and poor bioavailability, and describes a screen that found fisetin derivatives with significantly enhanced activity in an in vitro neuroprotection model; the abstract does not name CMS121. A 2020 mouse paper identifies fatty acid synthase (FASN) as a molecular target of CMS121 and says it modulates lipid metabolism and reduces lipid peroxidation. A 2019 paper reports that CMS121 and J147, which it describes as distinct in structure, increased acetyl-CoA in cell culture and mice through inhibition of acetyl-CoA carboxylase 1 (ACC1), with neuroprotection and increased histone H3K9 acetylation in SAMP8 mice. The 2024 review by the discovering group says CMS121 was found by adding protection against oxytosis and ferroptosis to a cell-based screen for Alzheimer's drug candidates (PMID 39422940).

Participants / model
Cell lines; mice
Treatment
Cell culture; the in vivo route is not stated in the abstracts
Follow-up
not stated in the source
Study design
Original preclinical studies; review
Funding
not stated in the source

The mechanism is reported by the group that owns the patent. The 2012 abstract does not name CMS121.

Read the original source
Transgenic Alzheimer's mice: less cognitive loss, inflammation and lipid peroxidation

Animal study

Ates G et al. Redox Biol. 2020;36:101648. PMID 32863221.

In transgenic Alzheimer's disease mice CMS121 alleviated cognitive loss, modulated lipid metabolism, and reduced inflammation and lipid peroxidation in the brain, and FASN was identified as a target. The abstract does not name the mouse line, the dose, the route or effect sizes.

Participants / model
Transgenic Alzheimer's disease mice
Treatment
CMS121; dose and route not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

This is the source for the less-neuroinflammation wording, and it is one mouse study from the discovering group.

Read the original source
SAMP8 fast-aging mice: cognition, aging markers, brain and kidney proteins, hearing

Animal study

Currais A et al. Elife. 2019;8. PMID 31742554.

In senescence-accelerated SAMP8 mice, CMS121 and J147 reduced cognitive decline and metabolic and transcriptional markers of aging in the brain, preserved mitochondrial homeostasis through acetyl-CoA metabolism, and increased H3K9 acetylation. When mice were fed J147 or CMS121 in the last quarter of their lifespan, both improved physiological markers for brain and kidney function, and drug treatment restored a more youthful protein profile in each organ (PMID 33550278). A collaboration with a hearing laboratory, in 16 female SAMP8 mice fed CMS121 in the diet, reported lower hearing thresholds at 12 kHz (39.8 versus 56.5, p = 0.044) and 16 kHz (43.8 versus 64.8, p = 0.040) at 13 weeks of age, and more preserved inner hair cell ribbon synapses (18.4 versus 15.7 per cell, p = 0.014) (PMID 37097512; the authors include Currais, Maher and Schubert).

Participants / model
SAMP8 mice, including 16 female SAMP8 mice in the hearing study
Treatment
CMS121 fed in the diet (stated in PMID 33550278 and PMID 37097512); doses and cognitive test details not in the abstracts
Follow-up
Last quarter of lifespan in the 2021 study; to 13 weeks of age in the hearing study
Study design
Original preclinical studies
Funding
not stated in the source

SAMP8 is an accelerated-aging model, not normal aging in mice or any result in people.

Read the original source
Huntington's disease, db/db and wild-type mice: motor function, survival, glucose, body weight

Animal study

Dafre AL et al. Aging (Albany NY). 2024;16(6):4980-4999. PMID 38517358.

In wild-type mice fed a CMS121 diet for 6 months, weight gain fell 40% and glucose and lipid indexes improved, with a higher resting metabolic rate. In R6/2 and YAC128 Huntington's disease mice, CMS121 slowed motor dysfunction and increased median life span, 'partially' attenuating disease, and the authors state CMS121 could provide some benefits for HD patients (PMID 37864765). In db/db mice fed CMS121 for 6 months, body weight fell 5% and glucose tolerance, HbA1c, insulin, triglycerides, liver inflammation markers and urine markers of kidney damage improved (PMID 37047807).

Participants / model
R6/2 and YAC128 Huntington's disease mice; db/db mice; wild-type mice
Treatment
CMS121 fed in the diet; 6 months in the db/db and wild-type studies; doses not stated in the abstracts
Follow-up
6 months in the db/db and wild-type studies; not stated for the Huntington's disease study
Study design
Original preclinical studies
Funding
not stated in the source

Reduced weight gain in non-obese animals is an effect that belongs with the results, because CMS121 is described as a brain-aging compound.

Read the original source
Registered Phase 1 in 99 healthy volunteers, aged 19 to 85, no posted results

Trial registry record

ClinicalTrials.gov. NCT05318040. Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion; United States.

A Phase 1 trial of escalating single and multiple oral doses of CMS121 and food effect in healthy volunteers. It is complete: start 2022-05-01, primary completion 2022-12-17, 99 participants enrolled (actual), ages 19 to 85, last record update 2023-02-16, and no results posted on the registry as of 2026-10-10. Design: randomized, double-blind, placebo-controlled single ascending doses in young adults, multiple ascending doses in young adults, multiple doses in elderly volunteers, and an open-label two-way crossover food-effect part. The primary outcome is treatment-emergent adverse events. Capsules were given orally. The condition field says Alzheimer Disease, but the volunteers were healthy.

Participants / model
Healthy volunteers aged 19 to 85; 99 enrolled (actual)
Treatment
Oral CMS121 capsules, single and multiple ascending doses, with a food-effect crossover part
Follow-up
Start 2022-05-01; primary completion 2022-12-17
Study design
Phase 1, randomized, double-blind, placebo-controlled ascending-dose parts plus an open-label food-effect crossover
Funding
Sponsor Virogenics, Inc.; collaborators National Institute on Aging and Celerion (registry record)

No results posted as of 2026-10-10. The trial tests safety and pharmacokinetics in healthy people, not efficacy, even though the condition field says Alzheimer Disease. Any later publication or results posting would need to be read before this page is updated.

Read the original source
2025 preprint, not peer reviewed: single doses to 1800 mg, 7-day doses to 900 mg per day, healthy adults

Human study

Maher P et al. medRxiv. 2025. PMID 40093210.

A 2025 medRxiv preprint by Maher, Christopher, Evans and Raschke reports single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days in healthy adults, 'generally well tolerated' with the majority of treatment-emergent adverse events mild. Pharmacokinetics of CMS121 and its metabolites rose in a dose-proportional or slightly greater than dose-proportional way, with the CMS121-C2 metabolite contributing most to molar-equivalent CMS121 in plasma, and minimal urinary excretion of metabolites. Elderly subjects had higher exposures and longer terminal half-lives, and exposure was about 50% higher in the fed state. The abstract states no adverse event counts, no QT or other cardiodynamic result and no sample size. The 2024 review abstract says it covers the toxicology testing that led to the IND approval and gives no results (PMID 39422940).

Participants / model
Healthy adults, including elderly subjects
Treatment
Oral CMS121, single doses up to 1800 mg and repeat doses up to 900 mg per day for 7 days
Follow-up
Single dose and 7 days of repeat dosing
Study design
Phase 1 healthy-volunteer study reported as a preprint; not peer reviewed in the records reviewed
Funding
not stated in the source

A preprint and not peer reviewed. The abstract does not name the registry number, so whether it reports NCT05318040 is not stated. No safety sentence beyond 'generally well tolerated' with mostly mild events is made here.

Read the original source
PubMed, 10 October 2026: 13 records, none gives CMS121 to a patient

PubMed search record

PubMed search run 10 October 2026: "CMS-121"[tiab] OR CMS121[tiab] OR "CMS 121"[tiab], with a follow-up screen of the records for human or trial terms (human, patients, volunteers, clinical, trial, randomized, phase 1 or 2).

The search returned 13 records, and abstracts were read for all 13. Eight carry human or trial terms; of those only the Phase 1 preprint reports people, and none reports CMS121 given to a patient, a cognitive outcome in a person, or a randomized efficacy trial. Three records use CMS121 or CMS-121 as a FASN or ACC1 inhibitor in cell work (HSV-1 infection, fatty liver cells, endothelial cells), and a fourth, a 2026 BCG trained-immunity paper (PMID 42642930), does not name CMS121 in its abstract; these are not evidence for the supplier claim. ClinicalTrials.gov queries for CMS121, 'CMS-121' and 'CMS121' OR 'CMS-121' OR 'VG-CMS121' each returned only NCT05318040, and queries for 'CMS121 fisetin derivative' and 'fisetin derivative Alzheimer' returned none.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature and registry search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source
Label searches, 10 October 2026: no label, no match

Regulatory record

U.S. Food and Drug Administration (DailyMed label search; openFDA Drugs@FDA query). Searches for CMS121, run 10 October 2026.

DailyMed returned no label for CMS121, and the openFDA Drugs@FDA query returned no match. ClinicalTrials.gov lists one study, NCT05318040, a completed Phase 1 trial in healthy volunteers.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated label and application search
Funding
not stated in the source

An absence finding as of 10 October 2026. It covers United States label and application records only.

Read the original source

Why is CMS-121 (CMS121) in C tier?

C fits a research compound with a wider preclinical package than most, including several mouse models, a defined molecular target and a completed registered Phase 1 trial. The data are thin where the claim lives: efficacy only in mice, almost all from the group linked to the patent holder, with no human efficacy data, no peer-reviewed human paper and no posted trial results.