What is CMS-121?
CMS-121 (also written CMS121) is a synthetic small molecule from the Salk Institute group of Pamela Maher, Antonio Currais and David Schubert, designed from the plant flavonoid fisetin. Rebuilding fisetin's core as a quinoline with a cyclopentyl ether gave compound 121, more than 400 times as potent as fisetin in an HT22 nerve cell death assay (Chiruta et al., 2012).
Later papers linked it to two enzymes of fatty acid synthesis, acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), and to protection of nerve cells from oxytosis/ferroptosis (Currais et al., 2019; Ates et al., 2020). It is an investigational compound, not an approved drug. Disguised Alpha supplies it as 25MG capsules, 60 per bottle, for laboratory research use only. Nothing on this page is guidance for use in people.
CMS-121 reference data
| Property | Value |
|---|---|
| Name | CMS-121 |
| Also called | CMS121, compound 121 (Chiruta et al., 2012), 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol, UNII BW9P9F8JEY (PubChem CID 135741221) |
| Structure | A quinoline ring with a 3,4-dihydroxyphenyl (catechol) group at position 2 and a cyclopentyloxy group at position 4; no amino acids |
| Compound class | Synthetic fisetin-derived quinoline (small molecule), studied in fatty acid synthesis and oxytosis/ferroptosis research |
| Molecular formula | C₂₀H₁₉NO₃ |
| Molecular weight | 321.4 g/mol |
| PubChem CID | 135741221 |
| Form | Capsules, 25MG per capsule, 60 capsules per bottle (1,500MG per bottle) |
| Testing | Third-party tested, with the certificate for each lot published on the product page and in the COA portal |
Format, strength and storage are from the product page, which lists no formula or weight. Those, the structure and the other names are from PubChem CID 135741221, whose formula matches the mass the 2012 paper reported for compound 121.
See it beside the other compounds on this site in the peptide molecular weight reference table.
What the research covers
Published work on CMS-121 falls into six areas. Each summary below states the model used. Apart from one phase 1 study, the evidence is cell and animal data. Every mouse study described below includes authors from the Salk laboratory that developed CMS-121, and the Salk Institute holds the patent (Currais et al., 2019).
Origin as a fisetin derivative
Fisetin was active in animal models of brain disorders but needed high concentrations in cell assays and had poor bioavailability. The Salk group screened derivatives against iodoacetic acid toxicity in HT22 cells, an in vitro ischemia model, then for glutathione maintenance, anti-inflammatory activity in N9 microglia and PC12 neurite outgrowth. Compound 121 kept all of these activities, and the catechol ring was essential in the quinoline series (Chiruta et al., 2012). A later paper says CMS-121 was selected from 160 synthetic fisetin derivatives (Ates et al., 2024). Models: nerve, microglial and PC12 cell lines.
Reported targets: ACC1, FASN and oxytosis/ferroptosis
Oxytosis is glutamate-triggered nerve cell death driven by glutathione depletion, lipoxygenase activation and reactive oxygen species; ferroptosis, named in 2012, shares its features (Maher et al., 2020). In HT22 cells and rat primary neurons, 1 µM CMS-121 raised ACC1 phosphorylation at serine 79, an inhibitory site set by AMPK; without AMPK, its protection against oxytosis fell. Blocking ACC1 with TOFA or siRNA protected HT22 cells from glutamate, and CMS-121 or ACC1 knockdown protected them from RSL3-induced ferroptosis (Currais et al., 2019).
A drug affinity screen in HT22 and HeLa cells then flagged FASN, and CMS-121 lowered FASN activity in HT22 lysates. CMS-121 or FASN knockdown raised HT22 survival after glutamate, erastin or RSL3 and lowered the lipid peroxidation marker 4-hydroxynonenal (4HNE). With FASN knocked down, CMS-121 still added protection against glutamate and erastin, but not RSL3 (Ates et al., 2020).
Independent laboratories use it as an ACC1 inhibitor in human endothelial cells (Chen et al., 2025) and as a FASN inhibitor in herpes simplex virus 1-infected SH-SY5Y cells (Albano et al., 2025). Models: cell lines and rat primary neurons.
Alzheimer's disease and aging mouse models
Male APPswe/PS1ΔE9 mice, an Alzheimer's disease model, were fed 400 ppm CMS-121 in their diet from 9 to 12 months of age. Spatial memory, disinhibition and contextual fear memory matched wild-type levels, with less hippocampal 4HNE, 15LOX2 and GFAP (Ates et al., 2020).
In female SAMP8 mice, a rapidly aging strain, the same diet from 9 to 13 months gave better reversal learning in the Barnes maze, more brain phospho-ACC1 and histone H3K9 acetylation, and cortical acetyl-CoA, α-ketoglutarate and succinate back at 9-month levels (Currais et al., 2019). Female SAMP8 mice fed 200 ppm from 4 to 13 weeks of age had significantly lower hearing thresholds at 12 and 16 kHz and more cochlear ribbon synapses than controls (Pham et al., 2023). Models: transgenic and senescence-accelerated mice.
Metabolic and kidney models
In female SAMP8 mice fed 400 ppm from 9 to 13 months, CMS-121 restored kidney weight, prevented the age-related rise in plasma creatinine and lowered kidney TNFα and NF-κB p65 (Kepchia et al., 2021). In male db/db mice, a leptin receptor-deficient model of type 2 diabetes, 6 months of CMS-121 in food from 5 weeks of age gave better glucose tolerance, lower HbA1c, insulin, triglycerides, free fatty acids and liver inflammation markers, and lower urinary NGAL, clusterin and albumin, markers of kidney damage (Zahid et al., 2023).
In wild-type male C57BL/6 mice on the same schedule, body weight gain was 40 percent lower than in control-fed mice, with better glucose and lipid indexes and more adipose mitochondrial markers; the authors proposed lower de novo lipogenesis as the link (Dafre et al., 2024). Models: SAMP8, db/db and C57BL/6 mice.
Huntington's disease mouse models
R6/2 mice, an aggressive Huntington's disease model, were fed 200 or 400 ppm CMS-121 from about 6 weeks of age. At 13 weeks, forelimb grip strength was significantly higher with 200 ppm, and median survival rose moderately but not significantly at that level only. In slower-progressing YAC128 mice, 200 ppm gave higher forelimb grip strength at 9 months, more open-field movement at 18 months and a 17 percent longer median survival (631 versus 540 days), without changing maximum survival (Ates et al., 2024). Models: R6/2 and YAC128 transgenic mice.
Phase 1 study in healthy adults
The developers' 2024 review describes the toxicology testing behind CMS-121's US Investigational New Drug application (Currais et al., 2024). The phase 1 study, registered as NCT05318040, gave single amounts and 7 days of repeated daily amounts to healthy adults, including an elderly cohort, plus a food-effect arm. CMS-121 was generally well tolerated, with mostly mild adverse events.
A metabolite, CMS121-C2, appeared to be the main CMS-121-related species in plasma; elderly subjects had higher exposure and longer half-lives; and food raised exposure by about 50 percent. The report is a preprint (Maher et al., 2025), and PubMed indexes no peer-reviewed version or later trial. Model: human phase 1 study.
Key studies
- Chiruta C, et al. "Chemical modification of the multitarget neuroprotective compound fisetin." J Med Chem. 2012. PMID 22192055. DOI 10.1021/jm2012563. HT22 cell screens: compound 121 over 400 times as potent as fisetin.
- Currais A, et al. "Elevating acetyl-CoA levels reduces aspects of brain aging." eLife. 2019. PMID 31742554. DOI 10.7554/eLife.47866. Old SAMP8 mice and nerve cells: ACC1 phosphorylation, acetyl-CoA, reversal learning.
- Ates G, et al. "CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation and alleviates cognitive loss in a transgenic mouse model of Alzheimer's disease." Redox Biol. 2020. PMID 32863221. DOI 10.1016/j.redox.2020.101648. APPswe/PS1ΔE9 mice and HT22 cells: FASN target, memory.
- Ates G, et al. "CMS121 Partially Attenuates Disease Progression in Mouse Models of Huntington's Disease." Mol Neurobiol. 2024. PMID 37864765. DOI 10.1007/s12035-023-03711-2. R6/2 and YAC128 mice: grip strength, median survival.
- Maher P, et al. "Safety, Pharmacokinetics, and Cardiodynamics of CMS121, a Novel Small Molecule Fisetin Derivative with Neuroprotective Properties, in Phase 1 Healthy Adult Volunteers." medRxiv (preprint). 2025. PMID 40093210. DOI 10.1101/2025.02.28.25323123. Healthy adults: generally well tolerated; preprint.
Handling and storage of CMS-121 capsules
General laboratory practice for this material:
- Store the sealed capsules at 15 to 25°C in the original container, away from moisture and direct light (storage guidance on the product page).
- Capsules ship in a sealed plastic or glass bottle or a resealable pouch, depending on the batch; close it after each opening.
- Record the lot number and keep its certificate; the CMS01 certificate confirms identity by LC-MS.
- For identity checks, compare data with C₂₀H₁₉NO₃ and 321.4 g/mol; the 2012 paper reported the protonated ion at m/z 322 (Chiruta et al., 2012).
Frequently asked questions
What is CMS-121?
CMS-121 is 4-(4-cyclopentyloxyquinolin-2-yl)benzene-1,2-diol, a synthetic quinoline designed from fisetin at the Salk Institute (Chiruta et al., 2012) and studied mainly in nerve cell death assays and mouse models of Alzheimer's disease (Currais et al., 2024).
Is CMS121 the same as CMS-121?
Yes. PubChem lists CMS121 and CMS-121 as names for one compound, CID 135741221. Most papers write CMS121 (Ates et al., 2020); some write CMS-121 (Chen et al., 2025).
Is CMS-121 a peptide?
No. It is a small synthetic molecule with no amino acids: a quinoline carrying a catechol ring and a cyclopentyl ether (Chiruta et al., 2012).
Is CMS-121 an ACC1 inhibitor or a FASN inhibitor?
Both labels appear. The developers first reported that it raises inhibitory ACC1 phosphorylation and acetyl-CoA through AMPK (Currais et al., 2019), then identified FASN as a target in a drug affinity screen (Ates et al., 2020). Both enzymes work in fatty acid synthesis.
Has CMS-121 been tested in people?
Only in one phase 1 study of healthy young and elderly adults, reported in a preprint as generally well tolerated (Maher et al., 2025). No efficacy trial is indexed in PubMed, and it is not an approved drug.
Where can researchers buy CMS-121?
Disguised Alpha sells CMS-121 for laboratory research as 25MG capsules, 60 per bottle, third-party tested with the certificate published on the product page: CMS-121.
Related compounds and guides
- J-147 research guide: a sister compound from the same Salk group
- Dihexa research guide
- Humanin research guide
- NAD+ research guide
- Glutathione research guide
- COA portal: every published certificate, by lot
This product is for research use only. It has not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.