J147
J147 has improved memory in some rodent experiments and extended lifespan in flies. Other animal experiments found no benefit. A completed 64-person oral phase I trial still has no posted results, and an intravenous stroke trial is recruiting. Human benefit and PK remain unknown.
Synthetic ATP5A-binding neurotrophic candidate
- J147 is a small molecule, not a peptide.
- A 64-person phase 1 completed in 2020 with no public results.
- A 2026 phase 2 uses intravenous J147 after stroke intervention, not oral nootropic use.
- Memory experiments include normal rodents and disease models, with both positive and null outcomes.
- The cited human record reports no half-life, Tmax, interaction, or efficacy result.
What exactly is J147?
J147 is a synthetic neurotrophic small-molecule drug candidate. FDA GSRS lists J147, while some public synonym databases attach a different CAS number. The cited FDA records list no Alzheimer's approval.
FDA GSRS · J147 identity
Government substance database
U.S. Food and Drug Administration. Global Substance Registration System, J147, UNII Z41H3C5BT9.
The record identifies J147 as C18H17F3N2O2, molecular weight 350.34 g/mol, and CAS 1807913-16-1.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
FDA GSRS and some secondary synonym databases attach different CAS mappings; the records should not be merged.
Read the original sourceHas J147 been tested in people?
A randomized 64-person single-ascending-dose phase 1 completed in 2020, but no results were posted. The registry therefore supplies no human adverse-event or PK values.
NCT03838185: completed oral single-dose phase I
Official trial registry or sponsor protocol
Abrexa Pharmaceuticals. NCT03838185. A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses of J147 in Healthy Young Volunteers and Healthy Elderly Volunteers. ClinicalTrials.gov. Completed February 1, 2020; record last updated September 3, 2020.
ClinicalTrials.gov lists 64 healthy participants and completed status, but no posted results. It therefore provides no dose-specific adverse events, human pharmacokinetic values, or efficacy outcome.
- Participants / model
- 64 healthy volunteers: younger men 18-50 and older men and women 60-85
- Treatment
- Single ascending oral J147 doses versus placebo under fasting conditions
- Follow-up
- Single-dose follow-up through about seven days; PK sampling to 48 hours
- Study design
- Randomized double-blind placebo-controlled phase 1 registry without results
- Funding
- Abrexa Pharmaceuticals
What does the 2026 stroke trial mean?
J147 entered a recruiting phase 2 trial as an intravenous emulsion after endovascular therapy for acute ischemic stroke. That is a new disease, route, and clinical question; it does not support oral anti-aging or Alzheimer's use.
NCT07430917: recruiting intravenous phase II stroke trial
Official trial registry or sponsor protocol
Abrexa Pharmaceuticals. NCT07430917. A Phase II, Randomized, Placebo-Controlled, Double-Blind, Adaptive Study to Assess the Safety and Efficacy of Intravenous J147 Combined With Endovascular Therapy in Patients With Acute Ischemic Stroke. ClinicalTrials.gov. Last updated August 24, 2026.
ClinicalTrials.gov lists recruiting status, an estimated 196 participants, and no posted results. This adaptive trial tests an intravenous emulsion in acute ischemic stroke with endovascular treatment. It is neither a completed efficacy study nor an oral Alzheimer or healthy-enhancement trial.
- Participants / model
- Planned 196 adults with acute ischemic stroke undergoing endovascular therapy
- Treatment
- Intravenous J147 emulsion or placebo after thrombectomy/endovascular therapy
- Follow-up
- Recruiting; primary completion planned 2028
- Study design
- Randomized double-blind adaptive phase 2 registry without results
- Funding
- Abrexa Pharmaceuticals
Does the memory evidence include healthy animals?
Yes. The original program reported better object recognition in normal rats and several memory measures in normal mice. Some learning outcomes were unchanged.
Normal-rat recognition experiments used roughly 12 animals per group. Mouse object-location, Y-maze and long-term Barnes retention results were positive; initial Barnes acquisition was nonsignificant and reversal was unaffected. Several figure-caption statistics are internally inconsistent, so the reported direction is more defensible than a precise universal effect size.
Later work in aged Alzheimer-model mice found selected behavioral improvements in small groups. Combination with donepezil was needed for some scopolamine-related fear outcomes. These models address different deficits and cannot establish a healthy-human memory benefit.
Chen et al., normal-rodent memory and AD prevention, 2011
Primary preclinical study
Chen Q, Prior M, Dargusch R, Roberts A, Riek R, Eichmann C, Chiruta C, Akaishi T, Abe K, Maher P, Schubert D. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease. PloS one. 2011. DOI 10.1371/journal.pone.0027865.
In normal rats, oral J147 increased novel-object recognition with approximately 12 animals per group. Normal-mouse experiments reported better object-location, Y-maze, and long-term Barnes retention, while initial Barnes acquisition and reversal did not improve. Rat slices showed facilitated LTP without a basal-transmission effect. Several figure-caption statistics conflict, so the reported direction is clearer than a precise effect estimate. Alzheimer-model groups were smaller, around 6 to 9 animals.
Read the original sourcePrior et al., late intervention in aged AD mice, 2013
Primary preclinical study
Prior M, Dargusch R, Ehren JL, Chiruta C, Schubert D. The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice. Alzheimer's research & therapy. 2013. DOI 10.1186/alzrt179.
Mice aged to 20 months were assigned to control feed (11) or J147 feed (13) for three months. Selected navigation, disinhibition and fear-conditioning outcomes improved. In the separate scopolamine comparison, J147 and donepezil improved different endpoints; contextual and cued fear improved only with the combination. Small groups, many comparisons, and model specificity limit translation, and human safety was not measured.
- Participants / model
- Aged APPswe/PS1ΔE9 transgenic mice; key groups approximately 11-12 animals
- Treatment
- J147 in feed at 200 ppm, estimated around 10 mg/kg/day
- Follow-up
- Three months
- Study design
- Controlled transgenic-mouse behavioral and pathology experiment
- Funding
- Salk Institute/Abrexa-linked development program
What supports the ATP-synthase and longevity claims?
Biochemical and cellular work supports ATP5A as a J147 target. Lifespan extension was measured in male fruit flies; the mouse aging work measured function and molecular changes rather than longer survival.
The fly study reported approximately 10 to 13% longer median lifespan, with an internal concentration-unit inconsistency. SAMP8 mouse studies found selected cognitive, vascular, inflammatory and molecular-aging changes. Later analyses overlap parts of that experimental program.
Late-life brain and kidney studies also compared J147 with CMS121. Their different organ effects cannot be pooled into a general rejuvenation result. The 2026 carbon-11 J147 imaging paper identified adipose tissue; a separate beta3 agonist activated brown fat. It does not show that ordinary J147 causes fat loss.
ATP5A target identification and fly lifespan, 2018
Primary preclinical study
Goldberg J, Currais A, Prior M, Fischer W, Chiruta C, Ratliff E, Daugherty D, Dargusch R, Finley K, Esparza-Moltó PB, Cuezva JM, Maher P, Petrascheck M, Schubert D. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging cell. 2018. DOI 10.1111/acel.12715.
Biochemical pull-down, target manipulation and cellular pathway work support ATP5A as a target. Male Drosophila median lifespan increased approximately 9.5% and 12.5 to 12.8% at the reported conditions. The paper inconsistently prints the higher concentration as micromolar in the figure and millimolar in prose, and differs slightly on the percentage; no exact transferable regimen should be inferred. SAMP8 transcriptomic/metabolomic drift measures are separate from survival. The mouse component does not prove mouse lifespan extension.
- Participants / model
- Cultured cells, bovine mitochondrial preparations, SAMP8 mice, and Drosophila; no treated humans
- Treatment
- J147 across in-vitro and animal experiments
- Follow-up
- Preclinical experiments
- Study design
- Target-identification and animal study
- Funding
- Salk/Abrexa-linked development program
Aging multiomics in SAMP8 mice, 2015
Primary preclinical study
Currais A, Goldberg J, Farrokhi C, Chang M, Prior M, Dargusch R, Daugherty D, Armando A, Quehenberger O, Maher P, Schubert D. A comprehensive multiomics approach toward understanding the relationship between aging and dementia. Aging. 2015. DOI 10.18632/aging.100838.
Selected cognition, synaptic, vascular, inflammatory, and molecular-aging measures moved toward a younger phenotype in an accelerated-aging mouse model. The study did not measure survival or effects in people, and later analyses overlap parts of the same experimental population.
Read the original sourceLate-life brain and kidney studies, 2021
Primary preclinical study
Kepchia D, Currais A, Dargusch R, Finley K, Schubert D, Maher P. Geroprotective effects of Alzheimer's disease drug candidates. Aging. 2021. DOI 10.18632/aging.202631.
J147 and CMS121 were compared in late-life SAMP8 experiments. Physiological/protein markers in brain and kidney improved in different ways. The compounds and organ endpoints must remain separate; the study tests tissue phenotypes rather than survival extension. It does not validate preventive treatment in healthy people.
Read the original sourceATP-synthase radiotracer and adipose imaging, 2026
Primary preclinical study
Jie CVML, Delparente A, Wang T, Reichert L, Krajnovic P, Schläppi M, Reininger L, Brandt LTL, Keller C, Orts J, Riek R, Krämer SD, Stoffel M, Wolfrum C, Schibli R, Mu L. ATP synthase is a promising target for identifying activated and non-activated adipose tissues. Nature communications. 2026. DOI 10.1038/s41467-026-71343-w.
Carbon-11-labeled J147 identified activated and nonactivated adipose tissues in mouse imaging, with competition/knockdown experiments supporting target recognition. Brown-fat activation used a separate beta3 agonist. The finding does not show that ordinary J147 activates brown fat or causes weight loss, and tracer exposure is not therapeutic exposure.
Read the original sourceWhat do we know about human safety and exposure?
The completed oral phase I registry reports 64 actual participants and no posted results. No dose-specific adverse-event table, human half-life or exposure curve can be extracted from that record.
Cell toxicology and selected negative genotoxicity tests do not establish a human therapeutic index. Rodent free-fatty-acid changes and microsome metabolism likewise cannot supply a human regimen or long-term safety assurance.
The recruiting intravenous phase II stroke trial estimates 196 participants and has no posted results. It is not an oral Alzheimer or healthy-enhancement trial.
J147 and liver free-fatty-acid metabolism, 2022
Primary preclinical study
Kepchia D, Huang L, Currais A, Liang Z, Fischer W, Maher P. The Alzheimer's disease drug candidate J147 decreases blood plasma fatty acid levels via modulation of AMPK/ACC1 signaling in the liver. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022. DOI 10.1016/j.biopha.2022.112648.
Lipidomics across three rodent experiments found lower plasma free fatty acids, linked to liver AMPK/ACC1 signaling and reduced synthesis in cell work. Reanalysis of existing experiments is not three new human studies. Lower FFA is not a measured fat-loss or endurance benefit.
Read the original sourceCeeTox and genotoxicity analysis
Primary preclinical study
Lapchak PA, Bombien R, Rajput PS. J-147 a Novel Hydrazide Lead Compound to Treat Neurodegeneration: CeeTox™ Safety and Genotoxicity Analysis. Journal of neurology & neurophysiology. 2013. DOI 10.4172/2155-9562.1000158.
Rat hepatoma cell assays estimated a sustained-toxicity concentration around 90 micromolar; selected genotoxicity tests were negative. Very large efficacy-to-toxicity ratios in that paper combine different experimental assays. They are not measured human therapeutic indices or proof of long-term safety.
Read the original sourceNCT03838185: completed oral single-dose phase I
Official trial registry or sponsor protocol
Abrexa Pharmaceuticals. NCT03838185. A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses of J147 in Healthy Young Volunteers and Healthy Elderly Volunteers. ClinicalTrials.gov. Completed February 1, 2020; record last updated September 3, 2020.
ClinicalTrials.gov lists 64 healthy participants and completed status, but no posted results. It therefore provides no dose-specific adverse events, human pharmacokinetic values, or efficacy outcome.
- Participants / model
- 64 healthy volunteers: younger men 18-50 and older men and women 60-85
- Treatment
- Single ascending oral J147 doses versus placebo under fasting conditions
- Follow-up
- Single-dose follow-up through about seven days; PK sampling to 48 hours
- Study design
- Randomized double-blind placebo-controlled phase 1 registry without results
- Funding
- Abrexa Pharmaceuticals
NCT07430917: recruiting intravenous phase II stroke trial
Official trial registry or sponsor protocol
Abrexa Pharmaceuticals. NCT07430917. A Phase II, Randomized, Placebo-Controlled, Double-Blind, Adaptive Study to Assess the Safety and Efficacy of Intravenous J147 Combined With Endovascular Therapy in Patients With Acute Ischemic Stroke. ClinicalTrials.gov. Last updated August 24, 2026.
ClinicalTrials.gov lists recruiting status, an estimated 196 participants, and no posted results. This adaptive trial tests an intravenous emulsion in acute ischemic stroke with endovascular treatment. It is neither a completed efficacy study nor an oral Alzheimer or healthy-enhancement trial.
- Participants / model
- Planned 196 adults with acute ischemic stroke undergoing endovascular therapy
- Treatment
- Intravenous J147 emulsion or placebo after thrombectomy/endovascular therapy
- Follow-up
- Recruiting; primary completion planned 2028
- Study design
- Randomized double-blind adaptive phase 2 registry without results
- Funding
- Abrexa Pharmaceuticals
Microsomes and mouse plasma · no human in-vivo PK
Preclinical metabolism study
Chiruta C, Zhao Y, Tang F, Wang T, Schubert D. Metabolism of a potent neuroprotective hydrazide. Bioorganic & Medicinal Chemistry. 2013;21(9):2733-2741. doi:10.1016/j.bmc.2013.03.020. PMID 23582448.
J147 metabolites were studied in human and mouse microsomes and in mouse plasma; the tested systems did not show release of the feared aromatic amine/hydrazine fragments under the reported conditions.
- Participants / model
- Human and mouse microsomes plus mouse plasma; no dosed human participants
- Treatment
- J147 in vitro and in mice
- Follow-up
- Preclinical metabolic assays
- Study design
- Microsomal and mouse metabolism study
- Funding
- Salk/Abrexa-linked development program
Human microsomes are not human clinical safety or PK, and absence of selected metabolites in these systems does not establish overall toxicology.
Read the original sourceWhy is J147 in D tier?
Mouse studies support several biological hypotheses. The completed phase 1 has no posted results, and the new intravenous stroke trial has no cognition or longevity outcome.
NCT03838185: completed oral single-dose phase I
Official trial registry or sponsor protocol
Abrexa Pharmaceuticals. NCT03838185. A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses of J147 in Healthy Young Volunteers and Healthy Elderly Volunteers. ClinicalTrials.gov. Completed February 1, 2020; record last updated September 3, 2020.
ClinicalTrials.gov lists 64 healthy participants and completed status, but no posted results. It therefore provides no dose-specific adverse events, human pharmacokinetic values, or efficacy outcome.
- Participants / model
- 64 healthy volunteers: younger men 18-50 and older men and women 60-85
- Treatment
- Single ascending oral J147 doses versus placebo under fasting conditions
- Follow-up
- Single-dose follow-up through about seven days; PK sampling to 48 hours
- Study design
- Randomized double-blind placebo-controlled phase 1 registry without results
- Funding
- Abrexa Pharmaceuticals
Prior et al., late intervention in aged AD mice, 2013
Primary preclinical study
Prior M, Dargusch R, Ehren JL, Chiruta C, Schubert D. The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice. Alzheimer's research & therapy. 2013. DOI 10.1186/alzrt179.
Mice aged to 20 months were assigned to control feed (11) or J147 feed (13) for three months. Selected navigation, disinhibition and fear-conditioning outcomes improved. In the separate scopolamine comparison, J147 and donepezil improved different endpoints; contextual and cued fear improved only with the combination. Small groups, many comparisons, and model specificity limit translation, and human safety was not measured.
- Participants / model
- Aged APPswe/PS1ΔE9 transgenic mice; key groups approximately 11-12 animals
- Treatment
- J147 in feed at 200 ppm, estimated around 10 mg/kg/day
- Follow-up
- Three months
- Study design
- Controlled transgenic-mouse behavioral and pathology experiment
- Funding
- Salk Institute/Abrexa-linked development program
ATP5A target identification and fly lifespan, 2018
Primary preclinical study
Goldberg J, Currais A, Prior M, Fischer W, Chiruta C, Ratliff E, Daugherty D, Dargusch R, Finley K, Esparza-Moltó PB, Cuezva JM, Maher P, Petrascheck M, Schubert D. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging cell. 2018. DOI 10.1111/acel.12715.
Biochemical pull-down, target manipulation and cellular pathway work support ATP5A as a target. Male Drosophila median lifespan increased approximately 9.5% and 12.5 to 12.8% at the reported conditions. The paper inconsistently prints the higher concentration as micromolar in the figure and millimolar in prose, and differs slightly on the percentage; no exact transferable regimen should be inferred. SAMP8 transcriptomic/metabolomic drift measures are separate from survival. The mouse component does not prove mouse lifespan extension.
- Participants / model
- Cultured cells, bovine mitochondrial preparations, SAMP8 mice, and Drosophila; no treated humans
- Treatment
- J147 across in-vitro and animal experiments
- Follow-up
- Preclinical experiments
- Study design
- Target-identification and animal study
- Funding
- Salk/Abrexa-linked development program
How consistent are the injury and mood results?
Rat and mouse studies reported benefits in some injury, mood, and neuropathy endpoints, with null results in others and some effects requiring co-treatment.
In a 2022 rat stroke paper, J147 reduced infarct volume in transient suture occlusion but was ineffective alone in embolic occlusion. Combining it with tPA improved several short-term outcomes. Abrexa funded the work and participated in PK and manuscript work; two authors were employees.
A 2024 traumatic-brain-injury study reported better later recovery after early treatment. A 2025 China-affiliated microglial paper added inflammatory-pathway findings. The abstract-level records do not provide enough denominator or safety detail to assess those results fully.
The postoperative Zucker-rat study found selected memory and metabolic improvements without an anti-inflammatory effect. A separate mood study reduced forced-swim and tail-suspension immobility but did not improve sucrose preference or novelty-suppressed feeding. Diabetic-neuropathy experiments found nerve-conduction and pain-response benefits in mice. None supplies a human mood or pain treatment effect.
J147 in rat ischemic stroke and tPA combination, 2022
Primary preclinical study
Jin R, Wang M, Zhong W, Kissinger CR, Villafranca JE, Li G. J147 Reduces tPA-Induced Brain Hemorrhage in Acute Experimental Stroke in Rats. Frontiers in neurology. 2022. DOI 10.3389/fneur.2022.821082.
Randomized rat experiments used blinded neurological/histological assessments. J147 reduced infarct volume in transient suture occlusion but was ineffective alone in embolic occlusion. Combining it with tPA reduced infarct/neurological deficits and delayed-tPA-associated hemorrhage at 72 hours. Thus monotherapy and combination results depend on the model. Abrexa funded the work and participated in PK/manuscript revision; two authors were company employees.
Read the original sourceJ147 in controlled cortical-impact TBI, 2024
Primary preclinical study
Jin R, Wang M, Shukla M, Lei Y, An D, Du J, Li G. J147 treatment protects against traumatic brain injury by inhibiting neuronal endoplasmic reticulum stress potentially via the AMPK/SREBP-1 pathway. Translational research : the journal of laboratory and clinical medicine. 2024. DOI 10.1016/j.trsl.2024.08.007.
Oral treatment began one hour after injury and continued for 3 to 7 days; behavioral assessments extended to day 35. The abstract reports improved functional recovery and reduced neuronal ER-stress-related injury in this exact-compound post-injury experiment. It does not report the denominator, allocation method, or complete toxicity data.
Read the original sourcePeking University/China-affiliated microglial study, 2025
Primary preclinical study
He L, Ali T, Wei T, Yin H, Yang Y, Zhao Z, Liu H, Tan Z. J147 modulates microglial polarization via CAMKK2/AMPK signaling to ameliorate neuroinflammation. Biochemical and biophysical research communications. 2025. DOI 10.1016/j.bbrc.2025.152395.
In LPS models and microglia/oligodendrocyte systems, J147 reduced selected inflammatory signals and shifted polarization markers; pharmacological CAMKK2/AMPK inhibition blocked effects. These inhibitors are not a complete specificity proof. Cell percentages and M1/M2 markers are not human cognition or recovery outcomes. The abstract does not report full sample allocation, quantitative behavioral outcomes, or complete adverse-event data.
Read the original sourceJ147 after surgery in Zucker rats, 2024
Primary preclinical study
Oberman K, van Leeuwen BL, Nabben M, Villafranca JE, Schoemaker RG. J147 affects cognition and anxiety after surgery in Zucker rats. Physiology & behavior. 2024. DOI 10.1016/j.physbeh.2023.114413.
Chronic exposure improved anxiety/short-term spatial memory and glucose sensitivity; acute exposure affected different memory/circadian endpoints. No anti-inflammatory effect was detected. Surgery did not cause extensive postoperative cognitive dysfunction in this model, so claims of broad POCD rescue overstate it. This is important evidence that the mechanism and outcomes are not uniformly positive.
Read the original sourceJ147 in diabetic neuropathy
Primary preclinical study
Daugherty DJ, Marquez A, Calcutt NA, Schubert D. A novel curcumin derivative for the treatment of diabetic neuropathy. Neuropharmacology. 2018. DOI 10.1016/j.neuropharm.2017.11.007.
In streptozotocin-diabetic mice, chronic treatment protected against nerve-conduction slowing and single exposures transiently reversed touch-evoked allodynia. These are relevant preclinical functional endpoints, not generic biomarker changes, but remain diabetes-model results without a human pain trial.
Read the original sourceMonoamines and rodent antidepressant-like behavior, 2021
Primary preclinical study
Pan X, Chen L, Xu W, Bao S, Wang J, Cui X, Gao S, Liu K, Avasthi S, Zhang M, Chen R. Activation of monoaminergic system contributes to the antidepressant- and anxiolytic-like effects of J147. Behavioural brain research. 2021. DOI 10.1016/j.bbr.2021.113374.
Three-day treatment reduced immobility in forced-swim/tail-suspension tests but did not improve sucrose preference or novelty-suppressed feeding. Brain monoamine levels and MAO-A activity changed at the higher exposure. These findings support mechanistic questions and interaction research; they do not establish human antidepressant efficacy or a clinical MAOI interaction rule.
Read the original sourceStudies and sources
FDA GSRS · J147 identity
Government substance database
U.S. Food and Drug Administration. Global Substance Registration System, J147, UNII Z41H3C5BT9.
The record identifies J147 as C18H17F3N2O2, molecular weight 350.34 g/mol, and CAS 1807913-16-1.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Not applicable
- Study design
- Primary source record
FDA GSRS and some secondary synonym databases attach different CAS mappings; the records should not be merged.
Read the original sourceNCT03838185: completed oral single-dose phase I
Official trial registry or sponsor protocol
Abrexa Pharmaceuticals. NCT03838185. A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Oral Doses of J147 in Healthy Young Volunteers and Healthy Elderly Volunteers. ClinicalTrials.gov. Completed February 1, 2020; record last updated September 3, 2020.
ClinicalTrials.gov lists 64 healthy participants and completed status, but no posted results. It therefore provides no dose-specific adverse events, human pharmacokinetic values, or efficacy outcome.
- Participants / model
- 64 healthy volunteers: younger men 18-50 and older men and women 60-85
- Treatment
- Single ascending oral J147 doses versus placebo under fasting conditions
- Follow-up
- Single-dose follow-up through about seven days; PK sampling to 48 hours
- Study design
- Randomized double-blind placebo-controlled phase 1 registry without results
- Funding
- Abrexa Pharmaceuticals
NCT07430917: recruiting intravenous phase II stroke trial
Official trial registry or sponsor protocol
Abrexa Pharmaceuticals. NCT07430917. A Phase II, Randomized, Placebo-Controlled, Double-Blind, Adaptive Study to Assess the Safety and Efficacy of Intravenous J147 Combined With Endovascular Therapy in Patients With Acute Ischemic Stroke. ClinicalTrials.gov. Last updated August 24, 2026.
ClinicalTrials.gov lists recruiting status, an estimated 196 participants, and no posted results. This adaptive trial tests an intravenous emulsion in acute ischemic stroke with endovascular treatment. It is neither a completed efficacy study nor an oral Alzheimer or healthy-enhancement trial.
- Participants / model
- Planned 196 adults with acute ischemic stroke undergoing endovascular therapy
- Treatment
- Intravenous J147 emulsion or placebo after thrombectomy/endovascular therapy
- Follow-up
- Recruiting; primary completion planned 2028
- Study design
- Randomized double-blind adaptive phase 2 registry without results
- Funding
- Abrexa Pharmaceuticals
Prior et al., late intervention in aged AD mice, 2013
Primary preclinical study
Prior M, Dargusch R, Ehren JL, Chiruta C, Schubert D. The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice. Alzheimer's research & therapy. 2013. DOI 10.1186/alzrt179.
Mice aged to 20 months were assigned to control feed (11) or J147 feed (13) for three months. Selected navigation, disinhibition and fear-conditioning outcomes improved. In the separate scopolamine comparison, J147 and donepezil improved different endpoints; contextual and cued fear improved only with the combination. Small groups, many comparisons, and model specificity limit translation, and human safety was not measured.
- Participants / model
- Aged APPswe/PS1ΔE9 transgenic mice; key groups approximately 11-12 animals
- Treatment
- J147 in feed at 200 ppm, estimated around 10 mg/kg/day
- Follow-up
- Three months
- Study design
- Controlled transgenic-mouse behavioral and pathology experiment
- Funding
- Salk Institute/Abrexa-linked development program
ATP5A target identification and fly lifespan, 2018
Primary preclinical study
Goldberg J, Currais A, Prior M, Fischer W, Chiruta C, Ratliff E, Daugherty D, Dargusch R, Finley K, Esparza-Moltó PB, Cuezva JM, Maher P, Petrascheck M, Schubert D. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging cell. 2018. DOI 10.1111/acel.12715.
Biochemical pull-down, target manipulation and cellular pathway work support ATP5A as a target. Male Drosophila median lifespan increased approximately 9.5% and 12.5 to 12.8% at the reported conditions. The paper inconsistently prints the higher concentration as micromolar in the figure and millimolar in prose, and differs slightly on the percentage; no exact transferable regimen should be inferred. SAMP8 transcriptomic/metabolomic drift measures are separate from survival. The mouse component does not prove mouse lifespan extension.
- Participants / model
- Cultured cells, bovine mitochondrial preparations, SAMP8 mice, and Drosophila; no treated humans
- Treatment
- J147 across in-vitro and animal experiments
- Follow-up
- Preclinical experiments
- Study design
- Target-identification and animal study
- Funding
- Salk/Abrexa-linked development program
Microsomes and mouse plasma · no human in-vivo PK
Preclinical metabolism study
Chiruta C, Zhao Y, Tang F, Wang T, Schubert D. Metabolism of a potent neuroprotective hydrazide. Bioorganic & Medicinal Chemistry. 2013;21(9):2733-2741. doi:10.1016/j.bmc.2013.03.020. PMID 23582448.
J147 metabolites were studied in human and mouse microsomes and in mouse plasma; the tested systems did not show release of the feared aromatic amine/hydrazine fragments under the reported conditions.
- Participants / model
- Human and mouse microsomes plus mouse plasma; no dosed human participants
- Treatment
- J147 in vitro and in mice
- Follow-up
- Preclinical metabolic assays
- Study design
- Microsomal and mouse metabolism study
- Funding
- Salk/Abrexa-linked development program
Human microsomes are not human clinical safety or PK, and absence of selected metabolites in these systems does not establish overall toxicology.
Read the original sourceChen et al., normal-rodent memory and AD prevention, 2011
Primary preclinical study
Chen Q, Prior M, Dargusch R, Roberts A, Riek R, Eichmann C, Chiruta C, Akaishi T, Abe K, Maher P, Schubert D. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease. PloS one. 2011. DOI 10.1371/journal.pone.0027865.
In normal rats, oral J147 increased novel-object recognition with approximately 12 animals per group. Normal-mouse experiments reported better object-location, Y-maze, and long-term Barnes retention, while initial Barnes acquisition and reversal did not improve. Rat slices showed facilitated LTP without a basal-transmission effect. Several figure-caption statistics conflict, so the reported direction is clearer than a precise effect estimate. Alzheimer-model groups were smaller, around 6 to 9 animals.
Read the original sourceAging multiomics in SAMP8 mice, 2015
Primary preclinical study
Currais A, Goldberg J, Farrokhi C, Chang M, Prior M, Dargusch R, Daugherty D, Armando A, Quehenberger O, Maher P, Schubert D. A comprehensive multiomics approach toward understanding the relationship between aging and dementia. Aging. 2015. DOI 10.18632/aging.100838.
Selected cognition, synaptic, vascular, inflammatory, and molecular-aging measures moved toward a younger phenotype in an accelerated-aging mouse model. The study did not measure survival or effects in people, and later analyses overlap parts of the same experimental population.
Read the original sourceLate-life brain and kidney studies, 2021
Primary preclinical study
Kepchia D, Currais A, Dargusch R, Finley K, Schubert D, Maher P. Geroprotective effects of Alzheimer's disease drug candidates. Aging. 2021. DOI 10.18632/aging.202631.
J147 and CMS121 were compared in late-life SAMP8 experiments. Physiological/protein markers in brain and kidney improved in different ways. The compounds and organ endpoints must remain separate; the study tests tissue phenotypes rather than survival extension. It does not validate preventive treatment in healthy people.
Read the original sourceJ147 in rat ischemic stroke and tPA combination, 2022
Primary preclinical study
Jin R, Wang M, Zhong W, Kissinger CR, Villafranca JE, Li G. J147 Reduces tPA-Induced Brain Hemorrhage in Acute Experimental Stroke in Rats. Frontiers in neurology. 2022. DOI 10.3389/fneur.2022.821082.
Randomized rat experiments used blinded neurological/histological assessments. J147 reduced infarct volume in transient suture occlusion but was ineffective alone in embolic occlusion. Combining it with tPA reduced infarct/neurological deficits and delayed-tPA-associated hemorrhage at 72 hours. Thus monotherapy and combination results depend on the model. Abrexa funded the work and participated in PK/manuscript revision; two authors were company employees.
Read the original sourceJ147 in controlled cortical-impact TBI, 2024
Primary preclinical study
Jin R, Wang M, Shukla M, Lei Y, An D, Du J, Li G. J147 treatment protects against traumatic brain injury by inhibiting neuronal endoplasmic reticulum stress potentially via the AMPK/SREBP-1 pathway. Translational research : the journal of laboratory and clinical medicine. 2024. DOI 10.1016/j.trsl.2024.08.007.
Oral treatment began one hour after injury and continued for 3 to 7 days; behavioral assessments extended to day 35. The abstract reports improved functional recovery and reduced neuronal ER-stress-related injury in this exact-compound post-injury experiment. It does not report the denominator, allocation method, or complete toxicity data.
Read the original sourcePeking University/China-affiliated microglial study, 2025
Primary preclinical study
He L, Ali T, Wei T, Yin H, Yang Y, Zhao Z, Liu H, Tan Z. J147 modulates microglial polarization via CAMKK2/AMPK signaling to ameliorate neuroinflammation. Biochemical and biophysical research communications. 2025. DOI 10.1016/j.bbrc.2025.152395.
In LPS models and microglia/oligodendrocyte systems, J147 reduced selected inflammatory signals and shifted polarization markers; pharmacological CAMKK2/AMPK inhibition blocked effects. These inhibitors are not a complete specificity proof. Cell percentages and M1/M2 markers are not human cognition or recovery outcomes. The abstract does not report full sample allocation, quantitative behavioral outcomes, or complete adverse-event data.
Read the original sourceJ147 after surgery in Zucker rats, 2024
Primary preclinical study
Oberman K, van Leeuwen BL, Nabben M, Villafranca JE, Schoemaker RG. J147 affects cognition and anxiety after surgery in Zucker rats. Physiology & behavior. 2024. DOI 10.1016/j.physbeh.2023.114413.
Chronic exposure improved anxiety/short-term spatial memory and glucose sensitivity; acute exposure affected different memory/circadian endpoints. No anti-inflammatory effect was detected. Surgery did not cause extensive postoperative cognitive dysfunction in this model, so claims of broad POCD rescue overstate it. This is important evidence that the mechanism and outcomes are not uniformly positive.
Read the original sourceJ147 in diabetic neuropathy
Primary preclinical study
Daugherty DJ, Marquez A, Calcutt NA, Schubert D. A novel curcumin derivative for the treatment of diabetic neuropathy. Neuropharmacology. 2018. DOI 10.1016/j.neuropharm.2017.11.007.
In streptozotocin-diabetic mice, chronic treatment protected against nerve-conduction slowing and single exposures transiently reversed touch-evoked allodynia. These are relevant preclinical functional endpoints, not generic biomarker changes, but remain diabetes-model results without a human pain trial.
Read the original sourceMonoamines and rodent antidepressant-like behavior, 2021
Primary preclinical study
Pan X, Chen L, Xu W, Bao S, Wang J, Cui X, Gao S, Liu K, Avasthi S, Zhang M, Chen R. Activation of monoaminergic system contributes to the antidepressant- and anxiolytic-like effects of J147. Behavioural brain research. 2021. DOI 10.1016/j.bbr.2021.113374.
Three-day treatment reduced immobility in forced-swim/tail-suspension tests but did not improve sucrose preference or novelty-suppressed feeding. Brain monoamine levels and MAO-A activity changed at the higher exposure. These findings support mechanistic questions and interaction research; they do not establish human antidepressant efficacy or a clinical MAOI interaction rule.
Read the original sourceJ147 and liver free-fatty-acid metabolism, 2022
Primary preclinical study
Kepchia D, Huang L, Currais A, Liang Z, Fischer W, Maher P. The Alzheimer's disease drug candidate J147 decreases blood plasma fatty acid levels via modulation of AMPK/ACC1 signaling in the liver. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022. DOI 10.1016/j.biopha.2022.112648.
Lipidomics across three rodent experiments found lower plasma free fatty acids, linked to liver AMPK/ACC1 signaling and reduced synthesis in cell work. Reanalysis of existing experiments is not three new human studies. Lower FFA is not a measured fat-loss or endurance benefit.
Read the original sourceATP-synthase radiotracer and adipose imaging, 2026
Primary preclinical study
Jie CVML, Delparente A, Wang T, Reichert L, Krajnovic P, Schläppi M, Reininger L, Brandt LTL, Keller C, Orts J, Riek R, Krämer SD, Stoffel M, Wolfrum C, Schibli R, Mu L. ATP synthase is a promising target for identifying activated and non-activated adipose tissues. Nature communications. 2026. DOI 10.1038/s41467-026-71343-w.
Carbon-11-labeled J147 identified activated and nonactivated adipose tissues in mouse imaging, with competition/knockdown experiments supporting target recognition. Brown-fat activation used a separate beta3 agonist. The finding does not show that ordinary J147 activates brown fat or causes weight loss, and tracer exposure is not therapeutic exposure.
Read the original sourceCeeTox and genotoxicity analysis
Primary preclinical study
Lapchak PA, Bombien R, Rajput PS. J-147 a Novel Hydrazide Lead Compound to Treat Neurodegeneration: CeeTox™ Safety and Genotoxicity Analysis. Journal of neurology & neurophysiology. 2013. DOI 10.4172/2155-9562.1000158.
Rat hepatoma cell assays estimated a sustained-toxicity concentration around 90 micromolar; selected genotoxicity tests were negative. Very large efficacy-to-toxicity ratios in that paper combine different experimental assays. They are not measured human therapeutic indices or proof of long-term safety.
Read the original sourceWhy is J147 in D tier?
D: positive and null memory results in animals, plus fly lifespan data. The completed 64-person oral trial has no posted results. The recruiting intravenous stroke trial cannot yet answer the human benefit or safety questions.