--- title: "CMS121: Research & Side Effects | BodyHackGuide" url: https://www.bodyhackguide.co/compound/cms-121 description: "CMS121: mechanism, clinical studies & side effects." lang: en --- Skip to content Compare notes on r/BodyHackGuide (https://reddit.com/r/bodyhackguide) Compare notes with other researchers. Join r/BodyHackGuide (https://reddit.com/r/bodyhackguide) # CMS121 Longevity: https://www.bodyhackguide.co/wiki#cat-longevity Status Phase 1,, not approved for human use Evidence Not graded on a research bench yet CMS121 is a synthetic derivative of the flavonol fisetin, made at the Salk Institute for Biological Studies in La Jolla in the Cellular Neurobiology Laboratory of Pamela Maher and David Schubert, as part of a series of more than 160 fisetin derivatives. Reviewed 4 November 2026 01 Overview ## What CMS121 is CMS121 was selected because it protected nerve cells from oxytosis and ferroptosis, a form of regulated cell death driven by glutathione loss and lipid peroxidation, and because it reached the brain after oral dosing in mice (PMID: 22192055, PMID: 39422940). The reported molecular target of CMS121 is fatty acid synthase, identified by drug affinity responsive target stability in two cell lines, and mice given CMS121 show more acetyl-CoA and activation of the AMPK pathway through inhibition of acetyl-CoA carboxylase 1 (PMID: 32863221, PMID: 31742554). For efficacy, the evidence is in cells, flies and mice; ClinicalTrials.gov lists one registered human study of CMS121, a phase 1 safety and pharmacokinetic trial in 99 healthy volunteers that completed in December 2022 with no results posted (NCT05318040). ### How it works ### Where CMS121 came from The Salk group screened compounds for protection in cell models of age-associated toxicity rather than against a single Alzheimer's disease target, which led them to the dietary flavonol fisetin (PMID: 22192055). Fisetin's half-maximal effective concentration in cell assays of 2 to 5 micromolar, its low lipophilicity, its high topological polar surface area and its five hydrogen bond donors all sat outside the range usual for central nervous system drugs, so Chandramouli Chiruta and colleagues synthesized more than 160 derivatives across several chemical scaffolds and tested them in two neuroprotection assays while checking that they kept fisetin's other activities, such as maintenance of glutathione under stress (PMID: 22192055, PMID: 39422940). Of the six most promising derivatives, CMS121 had the best combination of potency, a peak brain level of 700 nanomolar after a single oral dose of 20 mg/kg in mice, and oral bioavailability of 59 percent (PMID: 39422940). BodyHackGuide's fisetin (https://www.bodyhackguide.co/compound/fisetin) guide covers the parent compound. Read the full mechanism Show less ### Oxytosis and ferroptosis Oxytosis, redescribed in fibroblasts in 2012 as ferroptosis, is a non-apoptotic regulated cell death in which glutathione is depleted, glutathione peroxidase 4 is inhibited, lipoxygenases are activated and iron-dependent lipid peroxidation kills the cell (PMID: 33176157). The Salk group used inducers of this pathway (including cystine deprivation, glutamate, erastin and RSL3) as the primary screen for CMS121 (PMID: 39422940). In the brains of transgenic Alzheimer's disease mice, CMS121 lowered lipid peroxidation and markers of neuroinflammation (PMID: 32863221). ### Fatty acid synthase and acetyl-CoA Drug affinity responsive target stability analysis in HT22 mouse hippocampal cells and HeLa cells identified fatty acid synthase as the only protein among the top three hits in both lines, CMS121 partially inhibited the enzyme's activity in cell lysates in a dose-dependent way, and knocking fatty acid synthase down reproduced both the protection against oxytosis and ferroptosis and the anti-inflammatory effect in stimulated microglia (PMID: 32863221, PMID: 39422940). In rapidly aging SAMP8 mice, CMS121 and the structurally unrelated Salk compound J147 raised acetyl-CoA by inhibiting acetyl-CoA carboxylase 1, increased acetylation of histone H3K9 and preserved mitochondrial markers (PMID: 31742554). In primary mouse cortical neurons, CMS121 raised phosphorylated AMPK, phosphorylated acetyl-CoA carboxylase 1 and phosphorylated ULK1 and raised acetyl-CoA levels; how inhibiting fatty acid synthase activates AMPK is described as under investigation (PMID: 39422940). BodyHackGuide's J147 (https://www.bodyhackguide.co/compound/j-147) guide covers the companion compound from the same laboratory. ### Pharmacokinetics in people In the phase 1 trial, exposure to CMS121 and its metabolites rose with dose in a roughly dose-proportional way, the metabolite labelled CMS121-C2 contributed more of the molar-equivalent CMS121 in plasma than the parent compound, urinary excretion of metabolites was minimal, exposure was higher and terminal half-lives longer in elderly participants than in young adults, and exposure in the fed state was about 50 percent higher than fasting. These results are from a preprint that has not been peer reviewed, and no results have been posted on ClinicalTrials.gov (PMID: 40093210; NCT05318040). ### Studied for - Alzheimer's disease - Geroscience - Oxytosis and ferroptosis - Fatty acid synthase and lipid metabolism - Diabetic kidney disease - Age-related hearing loss ### Benefits listed - Spatial memory in a two-day water maze and contextual memory in fear conditioning in APPswe/PS1dE9 transgenic mice treated after cognitive impairment had developed (PMID: 32863221) - Brain lipid peroxidation and neuroinflammation markers in the same transgenic mice (PMID: 32863221) - Barnes maze and plus maze behaviour in 13-month-old SAMP8 mice, restored to the level of 9-month-old controls (PMID: 31742554) - Metabolic and gene transcription markers of brain aging in SAMP8 mice (PMID: 31742554) Show 7 more Show less - Survival of male Drosophila, 8.46 percent longer at 5 micromolar (PMID: 33550278) - Kidney weight and plasma creatinine in 13-month-old SAMP8 mice (PMID: 33550278) - Glucose tolerance, glycated hemoglobin, insulin and blood lipids in db/db mice (PMID: 37047807) - Urine albumin, clusterin and NGAL, markers of kidney damage, in db/db mice (PMID: 37047807) - Body weight gain in wild-type mice, 40 percent lower over 6 months of treated diet (PMID: 38517358) - Auditory brainstem response thresholds at 12 and 16 kHz and inner hair cell ribbon synapse counts in SAMP8 mice (PMID: 37097512) - Motor function and median lifespan in R6/2 and YAC128 mouse models of Huntington's disease (PMID: 37864765) 02 Research Free with email ## What the research shows No research bench grades CMS121 yet. Benches compare compounds people pair, with the evidence for each. ### Unlock the research summary Enter your email to keep reading. It is free, and it opens these sections on every compound page in this browser. - A summary of the key research - Safety and side effects - A link to the PubMed results You also get the free peptide cheat sheet by email. Unsubscribe anytime. Have an account? Sign in (https://www.bodyhackguide.co/auth) 03 Safety ## CMS121 side effects and interactions ### Side effects #### Common - No peer-reviewed human adverse event data exist for CMS121 - A preprint of the phase 1 trial, which has not been peer reviewed, reports that most treatment-emergent adverse events were mild in severity (PMID: 40093210) - Lower weight gain in male rats at 300 and 1,000 mg/kg a day for 28 days (PMID: 39422940) - Vomiting, loose or watery feces and reddish feces in dogs at 75 mg/kg a day and above (PMID: 39422940) #### Serious events - Microscopic kidney changes, with higher creatinine and blood urea nitrogen in one dog, at 75 mg/kg a day for 28 days; judged adverse (PMID: 39422940) - Smaller spleen and thymus, hepatocellular vacuolation, ileal mucosal hemorrhage and lymphoid depletion in dogs at 300 mg/kg a day for 14 days (PMID: 39422940) - No human data beyond 7 days of dosing, and no reproductive, long-term or drug interaction data in people (NCT05318040; PMID: 40093210) ### Who should not use it Contraindications None can be stated from human data, because the only human study of CMS121 is a phase 1 trial in healthy volunteers and its results have not been published in a peer-reviewed journal (NCT05318040; PMID: 40093210). Read all the contraindications and cautions Show less CMS121 is not an approved medicine: it has no approval anywhere and no established human use. The phase 1 trial excluded volunteers with clinically relevant cardiovascular, hematological, psychiatric, gastrointestinal, hepatic, renal, rheumatologic, autoimmune, endocrine, pulmonary, neurologic or dermatologic disease, anyone with a history of drug-associated skin rash, anyone with a condition or prior surgery that could interfere with drug absorption, anyone taking prescription or non-prescription medicines, herbal remedies or vitamin supplements within 14 days, anyone taking significant inducers of cytochrome P450 enzymes or P-glycoprotein within 28 days, and anyone with an estimated glomerular filtration rate at or below 80 mL/min/1.73 m2, or 70 in the elderly group (NCT05318040). Those exclusions indicate where the sponsor expected uncertainty. In dogs, microscopic kidney changes and higher creatinine and blood urea nitrogen in one dog at 75 mg/kg a day for 28 days were judged adverse and set the dog no-observed-adverse-effect level at 30 mg/kg a day (PMID: 39422940). The mechanism is a reason for caution: the reported target is fatty acid synthase, an enzyme of fatty acid synthesis present in many tissues, and the compound acts by partially inhibiting it (PMID: 32863221). No human study has examined what sustained inhibition does outside the brain. ### Interactions Not in our record Our record lists no interactions for CMS121. That means none are recorded here, not that none exist. This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds. Need bloodwork before starting? Full hormone + metabolic panels from Anabolic Insights. Code CHONCH for first-order discount. Order Bloodwork (https://anabolicinsights.ai/?ref=nwm2zjb) 04 Dosing Free with email ## Dosing No dose on record Our record lists no dose for CMS121. This section holds what it does list. ### Unlock the Dosing section - Route 05 Prices ## CMS121 prices No listings We do not track a vendor for CMS121 yet, so this page states no price. 06 Chemistry ## Chemistry and structure Molecular formula C20H19NO3 Molecular mass 321.4 g/mol CAS number 1353224-53-9 Half-life No peer-reviewed human value. A 2025 preprint of the phase 1 study reports that terminal elimination half-lives of CMS121 and its metabolites were longer in elderly participants than in young adults but does not give a single figure in its abstract, and no results have been posted on ClinicalTrials.gov (PMID: 40093210; NCT05318040). View on PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/135741221) 07 Related ## Related to CMS121 ### In the same category - 17-alpha-EstradiolPhase 4 for topical use in hair loss 17-alpha-estradiol (alfatradiol) is a naturally occurring steroid estrogen, the C17 epimer of the main estrogen 17beta-estradiol, that extends lifespan in male mice, where it causes only mild feminizing effects.: https://www.bodyhackguide.co/compound/alpha-estradiol - AcarbosePhase 4 Acarbose is a prescription alpha-glucosidase inhibitor for type 2 diabetes, a complex oligosaccharide produced by fermentation of the bacterium Actinoplanes utahensis, that slows the digestion of starch and table sugar in the small intestine (US prescribing information for Precose).: https://www.bodyhackguide.co/compound/acarbose - Alpha-Ketoglutarate (AKG)Phase 2 Alpha-ketoglutarate (AKG, also called 2-oxoglutarate) is an intermediate of the tricarboxylic acid (Krebs) cycle that cells make from isocitrate and from glutamate, and its calcium salt (Ca-AKG) is the form used in the main aging studies in mice and people.: https://www.bodyhackguide.co/compound/alpha-ketoglutarate-akg - CanagliflozinPhase 4 Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a C-glucoside discovered by chemists at Mitsubishi Tanabe Pharma, that lowers blood glucose in type 2 diabetes by making the kidneys excrete glucose in the urine; the FDA approved canagliflozin in 2013 as Invokana.: https://www.bodyhackguide.co/compound/canagliflozin - CortagenPreclinical Cortagen is a synthetic tetrapeptide, Ala-Glu-Asp-Pro (AEDP), made at Vladimir Khavinson's St. Petersburg Institute of Bioregulation and Gerontology from the amino acid analysis of Cortexin, a peptide preparation from the brain cortex.: https://www.bodyhackguide.co/compound/cortagen - NAD+Phase 2 NAD+ (nicotinamide adenine dinucleotide, oxidized form) is a pyridine dinucleotide coenzyme essential to energy metabolism, DNA repair via PARP enzymes, sirtuin-mediated gene regulation, and calcium signaling via CD38.: https://www.bodyhackguide.co/compound/nad All compounds (https://www.bodyhackguide.co/wiki) ### Compare CMS121 - Alternatives to CMS121: https://www.bodyhackguide.co/alternatives-to/cms-121 ### Research tools - Peptide Calculator Reconstitution and syringe units: https://www.bodyhackguide.co/tools/reconstitution - Reconstitution Guide How to mix, step by step: https://www.bodyhackguide.co/guides/how-to-reconstitute-peptides - Nasal Spray Calc mL per actuation: https://www.bodyhackguide.co/tools/intranasal - Half-Life Visualizer Decay curves: https://www.bodyhackguide.co/tools/halflife All articles (https://www.bodyhackguide.co/blog) 08 Questions ## Frequently asked questions What is CMS121? CMS121 is a synthetic derivative of the dietary flavonol fisetin, made at the Salk Institute for Biological Studies in La Jolla from a series of more than 160 fisetin derivatives (PMID: 22192055, PMID: 39422940). CMS121 was chosen because it protected nerve cells against oxytosis and ferroptosis more potently than fisetin and reached a peak brain level of 700 nanomolar after a single oral dose in mice (PMID: 39422940). The reported molecular target of CMS121 is fatty acid synthase (PMID: 32863221). Has CMS121 been tested in humans? CMS121 has one registered human study, a phase 1 randomized, double-blind, placebo-controlled trial of single and repeat doses in 99 healthy volunteers that completed on 17 December 2022 and has no results posted on ClinicalTrials.gov (NCT05318040). The sponsor of that CMS121 trial is Virogenics, Inc., with the National Institute on Aging and Celerion as collaborators (NCT05318040). A 2025 preprint from the sponsor reports that CMS121 was generally well tolerated at single doses up to 1,800 mg and repeat doses up to 900 mg a day for 7 days, with most adverse events mild, but that report has not been peer reviewed (PMID: 40093210). No human trial has tested whether CMS121 does anything for aging, memory or any disease. How is CMS121 different from fisetin? CMS121 was built from fisetin to fix properties that make fisetin a poor drug candidate: fisetin needed 2 to 5 micromolar in cell assays, had low lipophilicity, a high polar surface area and five hydrogen bond donors (PMID: 22192055). CMS121 is more potent in the two cell neuroprotection assays used for selection and had 59 percent oral bioavailability in mice, where fisetin's parent properties suggested poor absorption (PMID: 39422940). Fisetin is sold as a dietary supplement while CMS121 is an investigational compound with no approval anywhere. BodyHackGuide's fisetin (https://www.bodyhackguide.co/compound/fisetin) guide covers the flavonol that CMS121 was built from. What does CMS121 do in animals? In APPswe/PS1dE9 transgenic mice started on treatment at 9 months, when cognitive impairment was already present, CMS121 in the diet for 3 months preserved performance on memory tests and lowered brain lipid peroxidation and neuroinflammation (PMID: 32863221). CMS121, given to rapidly aging SAMP8 mice from 9 to 13 months, kept behaviour at the level of younger controls and reduced metabolic and transcriptional markers of brain aging (PMID: 31742554). In db/db diabetic mice, 6 months of CMS121 improved glucose tolerance and lowered markers of liver inflammation and kidney damage (PMID: 37047807), and in R6/2 and YAC128 Huntington's disease mice it slowed motor decline and increased median lifespan (PMID: 37864765). CMS121 at 5 micromolar increased survival of male fruit flies by 8.46 percent (PMID: 33550278). Is CMS121 safe? CMS121 has no published peer-reviewed human safety data; the phase 1 trial's results exist only as a preprint reporting that most treatment-emergent adverse events were mild (PMID: 40093210; NCT05318040). In animal testing, CMS121 was negative in a bacterial mutation assay and in a human lymphocyte chromosomal aberration assay, and single oral doses up to 1,000 mg/kg in rats caused no change in a functional observation battery (PMID: 39422940). The 28-day no-observed-adverse-effect level for CMS121 was 1,000 mg/kg a day in rats but only 30 mg/kg a day in dogs, where higher doses caused vomiting, loose feces and microscopic kidney changes (PMID: 39422940). No data exist on CMS121 beyond 7 days of human dosing, in pregnancy, in children or with other drugs. Can you buy CMS121? CMS121 is not an approved medicine in any country and is not a dietary supplement ingredient. Searches of Drugs@FDA, the FDA drug label database and the National Drug Code directory through the openFDA application programming interface on 27 October 2026 returned no product containing CMS121. The FDA holds a substance identifier for CMS121 in its Global Substance Registration System (UNII BW9P9F8JEY), which names a substance rather than approving a product. Who is studying CMS121? Nearly all CMS121 research comes from one group, the Cellular Neurobiology Laboratory at the Salk Institute for Biological Studies, with Pamela Maher, Antonio Currais and David Schubert as recurring authors (PMID: 22192055, PMID: 31742554, PMID: 32863221, PMID: 33550278). The CMS121 development and toxicology review and the phase 1 preprint are coauthored with William Raschke of Virogenics, Inc., the company that sponsored the trial (PMID: 39422940, PMID: 40093210). A hearing study was run with the Department of Otolaryngology at the University of California San Diego (PMID: 37097512), and other laboratories use CMS121 as a tool inhibitor of the lipogenic enzymes rather than as a candidate treatment, as a fatty acid synthase inhibitor in a herpes simplex virus study (PMID: 40327680) and as an acetyl-CoA carboxylase 1 inhibitor in a fatty liver cell study (PMID: 38395901). Free 2026 Peptide Cheat Sheet (PDF) 38 compounds and blends: vial sizes, BAC water volumes, dosing ranges and bloodwork markers. Download Free (https://www.bodyhackguide.co/guides/peptide-cheat-sheet-download) BodyHackGuide (https://www.bodyhackguide.co/) Your biohacking research hub: compound pricing, brain health protocols, dosing tools, and vendor reviews. support@bodyhackguide.co Join our Discord: https://discord.gg/Mhq5UdRYBA r/BodyHackGuide on Reddit: https://reddit.com/r/BodyHackGuide **Affiliate Disclosure:** We rank every vendor on the same public, reproducible methodology (https://www.bodyhackguide.co/vendors/methodology). Full details in our affiliate disclosure (https://www.bodyhackguide.co/affiliate-disclosure). **Research Disclaimer:** All compounds listed are for laboratory and research purposes only. Not for human consumption. This site does not sell or ship any products. Always consult a qualified healthcare professional and comply with local regulations. © 2026 BodyHackGuide. All rights reserved. - Terms: https://www.bodyhackguide.co/terms - Privacy: https://www.bodyhackguide.co/privacy ## Structured data ```json [ { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://www.bodyhackguide.co/" }, { "@type": "ListItem", "position": 2, "name": "Compounds", "item": "https://www.bodyhackguide.co/compare" }, { "@type": "ListItem", "position": 3, "name": "CMS121" } ] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "CMS121", "description": "CMS121 is a synthetic derivative of the flavonol fisetin, made at the Salk Institute for Biological Studies in La Jolla in the Cellular Neurobiology Laboratory of Pamela Maher and David Schubert, as part of a series of more than 160 fisetin derivatives (PMID: 22192055, PMID: 39422940). CMS121 was selected because it protected nerve cells from oxytosis and ferroptosis, a form of regulated cell death driven by glutathione loss and lipid peroxidation, and because it reached the brain after oral dosing in mice (PMID: 22192055, PMID: 39422940). The reported molecular target of CMS121 is fatty acid synthase, identified by drug affinity responsive target stability in two cell lines, and mice given CMS121 show more acetyl-CoA and activation of the AMPK pathway through inhibition of acetyl-CoA carboxylase 1 (PMID: 32863221, PMID: 31742554). 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CMS121 was selected because it protected nerve cells from oxytosis and ferroptosis, a form of regulated cell death driven by glutathione loss and lipid peroxidation, and because it reached the brain after oral dosing in mice (PMID: 22192055, PMID: 39422940). The reported molecular target of CMS121 is fatty acid synthase, identified by drug affinity responsive target stability in two cell lines, and mice given CMS121 show more acetyl-CoA and activation of the AMPK pathway through inhibition of acetyl-CoA carboxylase 1 (PMID: 32863221, PMID: 31742554). For efficacy, the evidence is in cells, flies and mice; ClinicalTrials.gov lists one registered human study of CMS121, a phase 1 safety and pharmacokinetic trial in 99 healthy volunteers that completed in December 2022 with no results posted (NCT05318040).", "activeIngredient": "CMS121", "administrationRoute": "Oral", "mechanismOfAction": "Where CMS121 came from The Salk group screened compounds for protection in cell models of age-associated toxicity rather than against a single Alzheimer's disease target, which led them to the dietary flavonol fisetin (PMID: 22192055). Fisetin's half-maximal effective concentration in cell assays of 2 to 5 micromolar, its low lipophilicity, its high topological polar surface area and its five hydrogen bond donors all sat outside the range usual for central nervous system drugs, so Chandramouli Chiruta and colleagues synthesized more than 160 derivatives across several chemical scaffolds and tested them in two neuroprotection assays while checking that they kept fisetin's other activities, such as maintenance of glutathione under stress (PMID: 22192055, PMID: 39422940). Of the six most promising derivatives, CMS121 had the best combination of potency, a peak brain level of 700 nanomolar after a single oral dose of 20 mg/kg in mice, and oral bioavailability of 59 percent (PMID: 39422940). BodyHackGuide's fisetin guide covers the parent compound. Oxytosis and ferroptosis Oxytosis, redescribed in fibroblasts in 2012 as ferroptosis, is a non-apoptotic regulated cell death in which glutathione is depleted, glutathione peroxidase 4 is inhibited, lipoxygenases are activated and iron-dependent lipid peroxidation kills the cell (PMID: 33176157). The Salk group used inducers of this pathway (including cystine deprivation, glutamate, erastin and RSL3) as the primary screen for CMS121 (PMID: 39422940). In the brains of transgenic Alzheimer's disease mice, CMS121 lowered lipid peroxidation and markers of neuroinflammation (PMID: 32863221). Fatty acid synthase and acetyl-CoA Drug affinity responsive target stability analysis in HT22 mouse hippocampal cells and HeLa cells identified fatty acid synthase as the only protein among the top three hits in both lines, CMS121 partially inhibited the enzyme's activity in cell lysates in a dose-dependent way, and knocking fatty acid synthase down reproduced both the protection against oxytosis and ferroptosis and the anti-inflammatory effect in stimulated microglia (PMID: 32863221, PMID: 39422940). In rapidly aging SAMP8 mice, CMS121 and the structurally unrelated Salk compound J147 raised acetyl-CoA by inhibiting acetyl-CoA carboxylase 1, increased acetylation of histone H3K9 and preserved mitochondrial markers (PMID: 31742554). In primary mouse cortical neurons, CMS121 raised phosphorylated AMPK, phosphorylated acetyl-CoA carboxylase 1 and phosphorylated ULK1 and raised acetyl-CoA levels; how inhibiting fatty acid synthase activates AMPK is described as under investigation (PMID: 39422940). BodyHackGuide's J147 guide covers the companion compound from the same laboratory. Pharmacokinetics in people In the phase 1 trial, exposure to CMS121 and its metabolites rose with dose in a roughly dose-proportional way, the metabolite labelled CMS121-C2 contributed more of the molar-equivalent CMS121 in plasma than the parent compound, urinary excretion of metabolites was minimal, exposure was higher and terminal half-lives longer in elderly participants than in young adults, and exposure in the fed state was about 50 percent higher than fasting. These results are from a preprint that has not been peer reviewed, and no results have been posted on ClinicalTrials.gov (PMID: 40093210; NCT05318040).", "legalStatus": "Not approved for human use (research chemical)", "warning": "For research purposes only. Not for human consumption." } }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "What is CMS121?", "acceptedAnswer": { "@type": "Answer", "text": "CMS121 is a synthetic derivative of the dietary flavonol fisetin, made at the Salk Institute for Biological Studies in La Jolla from a series of more than 160 fisetin derivatives (PMID: 22192055, PMID: 39422940). CMS121 was chosen because it protected nerve cells against oxytosis and ferroptosis more potently than fisetin and reached a peak brain level of 700 nanomolar after a single oral dose in mice (PMID: 39422940). The reported molecular target of CMS121 is fatty acid synthase (PMID: 32863221)." } }, { "@type": "Question", "name": "Has CMS121 been tested in humans?", "acceptedAnswer": { "@type": "Answer", "text": "CMS121 has one registered human study, a phase 1 randomized, double-blind, placebo-controlled trial of single and repeat doses in 99 healthy volunteers that completed on 17 December 2022 and has no results posted on ClinicalTrials.gov (NCT05318040). The sponsor of that CMS121 trial is Virogenics, Inc., with the National Institute on Aging and Celerion as collaborators (NCT05318040). A 2025 preprint from the sponsor reports that CMS121 was generally well tolerated at single doses up to 1,800 mg and repeat doses up to 900 mg a day for 7 days, with most adverse events mild, but that report has not been peer reviewed (PMID: 40093210). No human trial has tested whether CMS121 does anything for aging, memory or any disease." } }, { "@type": "Question", "name": "How is CMS121 different from fisetin?", "acceptedAnswer": { "@type": "Answer", "text": "CMS121 was built from fisetin to fix properties that make fisetin a poor drug candidate: fisetin needed 2 to 5 micromolar in cell assays, had low lipophilicity, a high polar surface area and five hydrogen bond donors (PMID: 22192055). CMS121 is more potent in the two cell neuroprotection assays used for selection and had 59 percent oral bioavailability in mice, where fisetin's parent properties suggested poor absorption (PMID: 39422940). Fisetin is sold as a dietary supplement while CMS121 is an investigational compound with no approval anywhere. BodyHackGuide's fisetin guide covers the flavonol that CMS121 was built from." } }, { "@type": "Question", "name": "What does CMS121 do in animals?", "acceptedAnswer": { "@type": "Answer", "text": "In APPswe/PS1dE9 transgenic mice started on treatment at 9 months, when cognitive impairment was already present, CMS121 in the diet for 3 months preserved performance on memory tests and lowered brain lipid peroxidation and neuroinflammation (PMID: 32863221). CMS121, given to rapidly aging SAMP8 mice from 9 to 13 months, kept behaviour at the level of younger controls and reduced metabolic and transcriptional markers of brain aging (PMID: 31742554). In db/db diabetic mice, 6 months of CMS121 improved glucose tolerance and lowered markers of liver inflammation and kidney damage (PMID: 37047807), and in R6/2 and YAC128 Huntington's disease mice it slowed motor decline and increased median lifespan (PMID: 37864765). CMS121 at 5 micromolar increased survival of male fruit flies by 8.46 percent (PMID: 33550278)." } }, { "@type": "Question", "name": "Is CMS121 safe?", "acceptedAnswer": { "@type": "Answer", "text": "CMS121 has no published peer-reviewed human safety data; the phase 1 trial's results exist only as a preprint reporting that most treatment-emergent adverse events were mild (PMID: 40093210; NCT05318040). In animal testing, CMS121 was negative in a bacterial mutation assay and in a human lymphocyte chromosomal aberration assay, and single oral doses up to 1,000 mg/kg in rats caused no change in a functional observation battery (PMID: 39422940). The 28-day no-observed-adverse-effect level for CMS121 was 1,000 mg/kg a day in rats but only 30 mg/kg a day in dogs, where higher doses caused vomiting, loose feces and microscopic kidney changes (PMID: 39422940). No data exist on CMS121 beyond 7 days of human dosing, in pregnancy, in children or with other drugs." } }, { "@type": "Question", "name": "Can you buy CMS121?", "acceptedAnswer": { "@type": "Answer", "text": "CMS121 is not an approved medicine in any country and is not a dietary supplement ingredient. Searches of Drugs@FDA, the FDA drug label database and the National Drug Code directory through the openFDA application programming interface on 27 October 2026 returned no product containing CMS121. The FDA holds a substance identifier for CMS121 in its Global Substance Registration System (UNII BW9P9F8JEY), which names a substance rather than approving a product." } }, { "@type": "Question", "name": "Who is studying CMS121?", "acceptedAnswer": { "@type": "Answer", "text": "Nearly all CMS121 research comes from one group, the Cellular Neurobiology Laboratory at the Salk Institute for Biological Studies, with Pamela Maher, Antonio Currais and David Schubert as recurring authors (PMID: 22192055, PMID: 31742554, PMID: 32863221, PMID: 33550278). The CMS121 development and toxicology review and the phase 1 preprint are coauthored with William Raschke of Virogenics, Inc., the company that sponsored the trial (PMID: 39422940, PMID: 40093210). A hearing study was run with the Department of Otolaryngology at the University of California San Diego (PMID: 37097512), and other laboratories use CMS121 as a tool inhibitor of the lipogenic enzymes rather than as a candidate treatment, as a fatty acid synthase inhibitor in a herpes simplex virus study (PMID: 40327680) and as an acetyl-CoA carboxylase 1 inhibitor in a fatty liver cell study (PMID: 38395901)." } } ] }, { "@context": "https://schema.org", "@type": "Organization", "@id": "https://www.bodyhackguide.co#organization", "name": "BodyHackGuide", "alternateName": "BHG", "url": "https://www.bodyhackguide.co", "logo": { "@type": "ImageObject", "url": "https://www.bodyhackguide.co/logo.png", "width": 512, "height": 512 }, "description": "Evidence-based research reference for peptides and nootropics. 273 compound profiles, interactive dosing calculators, vendor price comparisons, and trust-scored vendor reviews scored on a public, reproducible methodology applied to every vendor. 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