CMS121

Overview

CMS121 is a non-peptide small-molecule quinoline, a synthetic analog of the natural flavonoid fisetin, developed to inhibit fatty acid synthase (FASN) and reduce lipid peroxidation in neuronal cells. It has completed a Phase 1 safety and pharmacokinetics trial in healthy volunteers (NCT05318040) but has no approved medical use and no published human efficacy data in Alzheimer's disease or any other condition. The compound is sold by research-chemical suppliers for laboratory use only; some direct-to-consumer vendors incorrectly market it as a "peptide" supplement despite its small-molecule structure.

Mechanism of Action

CMS121 was identified via drug affinity responsive target stability (DARTS) proteomics in HT22 neuronal and HeLa cells as a selective inhibitor of fatty acid synthase (FASN), the only protein in the top three targets for both cell lines. FASN inhibition reduces substrate availability for lipid peroxidation, lowering the peroxidation marker 4-hydroxynonenal (4-HNE) and downstream inflammatory mediators including 15-LOX2, GFAP, iNOS, COX2, and TNF-α in mouse hippocampus and cultured neuronal/microglial cells. Note: some commercial reagent suppliers label CMS121 as an acetyl-CoA carboxylase 1 (ACC1) inhibitor in catalog copy, but this designation does not appear in the peer-reviewed mechanistic literature, which identifies FASN as the validated target.

Research Summary

In APPswe/PS1dE9 double-transgenic mice (a model of Alzheimer's disease), dietary CMS121 (~34 mg/kg/day for 3 months starting at 9 months of age) normalized elevated hippocampal 4-HNE lipid-peroxidation adducts to wild-type levels, reduced 15-LOX2 and GFAP expression, and reversed cognitive deficits in Morris water maze testing to performance indistinguishable from wild-type mice. In vitro, CMS121 reduced iNOS, COX2, and TNF-α induction and blunted lipid-peroxidation increases in LPS-activated microglial cell cultures. A completed Phase 1 trial in approximately 100 healthy volunteers (NCT05318040) tested single oral doses up to 1800 mg and repeat doses up to 900 mg/day in young adults (600 mg/day in elderly subjects) for 7 days, reporting generally well-tolerated safety profiles with the majority of adverse events classified as mild; no serious adverse events were reported. Elderly subjects showed higher systemic exposure and longer terminal half-life than young adults, and fed-state exposure was approximately 50% higher than fasted with delayed absorption. No human efficacy data exist in Alzheimer's disease patients or any patient population.

Vendors selling CMS121

Scored vendors carrying CMS121, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.

Reported Side Effects

• Phase 1: majority of adverse events mild (93% of 149 total events)
• No serious adverse events reported in Phase 1 healthy volunteers
• Higher systemic exposure in elderly subjects
• Significant food-effect interaction (~50% increase fed vs. fasted)
• No chronic-use or drug-interaction safety data

Compare CMS121 with Others

Research References

• CMS-121 — PubChem Compound Summary for CID 135741221.
• 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. 2020. PMID 32713889.
• Safety, Pharmacokinetics, and Cardiodynamics of CMS121, a Novel Small Molecule Fisetin Derivative with Neuroprotective Properties, in Phase 1 Healthy Adult Volunteers. 2025. PMID 40093210.
• NCT05318040 — Safety, Tolerability and Pharmacokinetics of CMS121, a Drug Candidate for Alzheimer's Disease, in Healthy Subjects (ClinicalTrials.gov).

Frequently asked questions

Has CMS121 been independently lab-tested?

Disclosed Labs has collected 3 Certificates of Analysis (COA) for CMS121 from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 99.1% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/cms-121/testing.

What is the average purity of CMS121 on the market?

Based on 3 COAs analyzed by Disclosed Labs, CMS121 products average 99.1% (±0.0%) tested purity. Individual vendor results vary; see per-vendor COA data at https://www.disclosedlabs.com/peptides/cms-121/coas.

Where can researchers source CMS121?

1 vendor with Disclosed Labs trust grades currently list CMS121, including Kimera Chems. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/cms-121.

How does CMS121 work?

CMS121 was identified via drug affinity responsive target stability (DARTS) proteomics in HT22 neuronal and HeLa cells as a selective inhibitor of fatty acid synthase (FASN), the only protein in the top three targets for both cell lines. FASN inhibition reduces substrate availability for lipid peroxidation, lowering the peroxidation marker 4-hydroxynonenal (4-HNE) and downstream inflammatory mediators including 15-LOX2, GFAP, iNOS, COX2, and TNF-α in mouse hippocampus and cultured neuronal/microglial cells. Note: some commercial reagent suppliers label CMS121 as an acetyl-CoA carboxylase 1 (ACC1) inhibitor in catalog copy, but this designation does not appear in the peer-reviewed mechanistic literature, which identifies FASN as the validated target.

What does the research say about CMS121?

In APPswe/PS1dE9 double-transgenic mice (a model of Alzheimer's disease), dietary CMS121 (~34 mg/kg/day for 3 months starting at 9 months of age) normalized elevated hippocampal 4-HNE lipid-peroxidation adducts to wild-type levels, reduced 15-LOX2 and GFAP expression, and reversed cognitive deficits in Morris water maze testing to performance indistinguishable from wild-type mice. In vitro, CMS121 reduced iNOS, COX2, and TNF-α induction and blunted lipid-peroxidation increases in LPS-activated microglial cell cultures. A completed Phase 1 trial in approximately 100 healthy volunteers (NCT05318040) tested single oral doses up to 1800 mg and repeat doses up to 900 mg/day in young adults (600 mg/day in elderly subjects) for 7 days, reporting generally well-tolerated safety profiles with the majority of adverse events classified as mild; no serious adverse events were reported. Elderly subjects showed higher systemic exposure and longer terminal half-life than young adults, and fed-state exposure was approximately 50% higher than fasted with delayed absorption. No human efficacy data exist in Alzheimer's disease patients or any patient population.