Clinical Phase 1Neuroprotection & LongevityNot a peptide — synthetic research compound

CMS121

Synthetic fisetin derivative (flavonoid analog) – not a peptide, small molecule · CMS-121, Fisetin-Derivat CMS121 · CAS no. 1353224-53-9

CMS121 is a synthetic small molecule (not a peptide) that was optimized at the Salk Institute from the natural flavonoid fisetin. In research it is classified as a "geroneuroprotector" – that is, a substance intended to address not a single disease feature but the aging processes of the nervous system. At its core is the inhibition of the oxytotic/ferroptotic cell-death pathway: CMS121 is intended to reduce lipid peroxidation and oxidative stress and to preserve mitochondrial function. In animal models (Alzheimer-transgenic mice as well as fast-aging SAMP8 mice) improved memory performance and slowed neuronal degeneration have been reported. A first first-in-human Phase 1 safety test in healthy adults has since been completed and published; this does not, however, demonstrate efficacy in humans.

Machine-assisted translation. The German original is the authoritative version.

At a glance

Substance class: Synthetic fisetin derivative (flavonoid analog), small molecule – not a peptide
Origin: Salk Institute, Schubert/Maher laboratory; clinical development: Virogenics, Inc.
CAS number: 1353224-53-9
Concept: "Geroneuroprotector" – targets brain aging instead of a single feature
Primary pathway: Inhibition of oxytosis/ferroptosis; protection against lipid peroxidation
Discussed target structures: Fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1)
Evidence base: Predominantly cell and animal models; Phase 1 safety in humans completed
Status (2026): Investigational; not approved as a medicinal product anywhere

Origin & development

CMS121 comes from the program of David Schubert and Pamela Maher at the Salk Institute (La Jolla, USA). The starting point was the observation that the natural flavonoid fisetin – contained in strawberries, among other things – protects cultured nerve cells and improves the memory of healthy mice. From chemically optimized fisetin variants, CMS121 emerged as a particularly effective candidate.

CMS121 stems from the same Salk program as the related molecule J-147 (also a non-peptide candidate). Unlike J-147 (which is linked to the company Abrexa), the clinical development of CMS121 was taken over by the biotech firm Virogenics, Inc., which carried the Phase 1 testing. Funding came, among others, from the US National Institute on Aging (NIH).

Mechanism: anti-ferroptosis and lipid protection

CMS121 was developed not via a classic disease target but via a cell-based phenotypic screen that protects against oxytotic/ferroptotic cell death. Ferroptosis is an iron- and lipid-peroxidation-dependent form of regulated cell death that is associated with aging and neurodegenerative toxicities.

Mechanistically, CMS121 is described as an inhibitor of fatty acid synthase (FASN); in addition, a rise in acetyl-CoA and a resulting inhibition of acetyl-CoA carboxylase 1 (ACC1) is reported. Through these interventions in lipid metabolism, excessive lipid peroxidation is intended to be reduced and mitochondrial homeostasis stabilized.

Inhibits the oxytosis/ferroptosis cell-death pathway (anti-ferroptotic)
Reduces oxidative stress and lipid peroxidation
Described targets: FASN and ACC1 in fatty acid/lipid metabolism
Intended to preserve mitochondrial function and acetyl-CoA metabolism
All mechanistic statements come from laboratory/animal models

Preclinical: Alzheimer's and aging models

In Alzheimer-transgenic mice, CMS121 reportedly reduced lipid peroxidation and inflammation in the brain and mitigated cognitive deficits. In fast-aging SAMP8 mice, CMS121 (and the related J-147) improved memory markers as well as metabolic and transcriptional signs of brain aging – a central finding of the 2019 eLife publication.

Further preclinical work describes effects beyond the brain, including on age- and metabolism-related changes. These results are from animal experiments and are not transferable to humans.

Alzheimer-transgenic mice: less lipid peroxidation/inflammation, better cognition (animal data)
SAMP8 aging model: improved memory and aging markers (eLife 2019)
Indications of effects outside the brain (metabolism) in disease models
Findings purely preclinical – no proof of benefit in humans

Status & context: first-in-human Phase 1

For CMS121, a first clinical Phase 1 trial (NCT05318040, sponsor Virogenics; single- and multiple-dose escalation in healthy adults) was conducted and completed. The results published in 2025 report that the tested amounts were generally well tolerated over several days and that most adverse events were mild; no deaths and no serious safety events were reported.

Important for context: a Phase 1 trial tests safety and pharmacokinetics in healthy subjects – it does not demonstrate efficacy in Alzheimer's or against aging. CMS121 thus remains an investigational molecule without approval. The robust efficacy data come from cell and animal models.

Phase 1 safety trial in healthy subjects completed (NCT05318040, Virogenics)
Report: generally well tolerated, predominantly mild side effects
Phase 1 = safety/pharmacokinetics, no proof of efficacy
Not approved as a medicinal product anywhere; sale as a "research chemical" is unregulated

Clinical trials

Phase 1NCT05318040 ↗

Safety, tolerability & pharmacokinetics in healthy subjects

Completed (published 2025)

Single- and multiple-dose escalation (SAD/MAD) in healthy adults; sponsor Virogenics. Report: generally well tolerated, predominantly mild events. A Phase 1 trial tests safety/pharmacokinetics – it does not demonstrate efficacy.

Regulatory status

General

Investigational / not approved

CMS121 is not an approved medicinal product and not a dietary supplement. A Phase 1 safety trial has been completed; there is no proof of efficacy or approval.

Germany (AMG)

Not approved

In Germany/the EU there is no approval. Use in humans outside of authorized clinical trials is not provided for under medicines law; offerings as a "research chemical" are not intended for human use.

Sport (WADA)

Not listed by name

CMS121 is not explicitly listed on the WADA prohibited list. Unapproved/investigational substances may, however, fall under the general clause on non-approved substances (S0); athletes should check this on their own responsibility.

Safety & context

Efficacy evidence comes almost exclusively from cell and animal models; transferability to humans is not established.
The completed Phase 1 trial tested only safety/tolerability in healthy subjects, not therapeutic benefit.
Long-term safety, interactions, and risks in the ill or aging human are not sufficiently investigated.
Material sold as a "research chemical" is not quality-tested and not intended for human use.
This profile serves information purposes only and contains no dosing or usage instructions.

Frequently asked questions

Is CMS121 a peptide?: No. CMS121 is a synthetic small molecule – a derivative derived from the plant flavonoid fisetin. It does not belong to the peptides but to the group of non-peptide research substances.
Is CMS121 an approved medication against Alzheimer's?: No. CMS121 is not approved as a medicinal product anywhere. A first Phase 1 safety trial in healthy volunteers has been completed, but there is no proof of efficacy in Alzheimer's or against aging in humans; the positive findings come from animal and cell models.
What does "geroneuroprotector" mean?: This is how the Salk group describes substances intended to address not a single disease feature but fundamental aging processes of the nervous system – for CMS121 above all via the inhibition of oxidative stress, lipid peroxidation, and ferroptosis. This is a research concept, not a proven clinical benefit.

Sources

This profile is for information and education only. It does not replace medical advice and deliberately contains no dosing, reconstitution, usage or sourcing information.

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