CMS‑121
Neuroprotective drug candidate engineered from fisetin, a FASN inhibitor, preclinical data only.
Pharmacology
Contents
WHAT IS CMS-121?
Detailed overview
CMS-121 is a synthetic derivative engineered at the Salk Institute from the plant flavonol fisetin, selected from roughly 160 analogues for improved stability and brain penetration. It inhibits fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1), reducing harmful lipid peroxidation, raising acetyl-CoA levels, and increasing H3K9 histone acetylation linked to memory genes, while protecting against oxytosis/ferroptosis cell death and neuroinflammation. In mouse models it slowed features of aging and Alzheimer's disease, improved cognition, and showed geroprotective and metabolic-protective effects. There is no human efficacy data: the compound is an experimental drug candidate only now entering early clinical testing.
Mechanism
FASN/ACC1 inhibitor, raises acetyl-CoA
Evidence
Preclinical (entering early human trials)
Origin
Fisetin derivative (Salk Institute)
Receptor profile
- Fatty acid synthase (FASN)Strong
- Acetyl-CoA carboxylase 1 (ACC1)Moderate
- Oxytosis / ferroptosis and neuroinflammationModerate
Safety
Side effects, stop signs, contraindications
Side effects · 4
- No published human safety data: evidence comes almost entirely from mouse and cell-based preclinical studies
- FASN and ACC1 inhibition could theoretically affect lipid metabolism, but the clinical relevance in humans is unknown
- Oral bioavailability, tissue distribution and long-term toxicity in humans are uncharacterized
- Experimental, unapproved drug candidate with an unknown side-effect spectrum
Contraindications · 4
- Pregnancy and breastfeeding: safety not established, avoid
- Not an approved medicine: not recommended for human use without clinical supervision
- Unknown drug interactions with agents affecting lipid metabolism or mitochondrial function
- Children and adolescents: no data, avoid
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
CMS121, a Novel Drug Candidate for the Treatment of Alzheimer's Disease and Age-Related Dementia.
Currais A, Raschke W, Maher P, et al.
CMS121: a novel approach to mitigate aging-related obesity and metabolic dysfunction.
Dafre AL, Schubert D, Maher P, et al.
CMS121 Partially Attenuates Disease Progression in Mouse Models of Huntington's Disease.
Ates G, Currais A, Maher P, et al.
The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice.
Zahid S, Dafre AL, Currais A, 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.
Ates G, Goldberg J, Currais A, Maher P
Elevating acetyl-CoA levels reduces aspects of brain aging.
Currais A, Huang L, Goldberg J, et al.
FAQ
FAQ
Neuroprotective drug candidate engineered from fisetin, a FASN inhibitor, preclinical data only.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.