CMS121 — ACC1 & FASN Modulator (GeroneuroProtective Small-Molecule)

CMS121 is a synthetic derivative of the flavonoid Fisetin, developed for research into neurodegeneration, metabolic dysfunction and age-related lipid dysregulation. It has shown promising activity in pre-clinical models involving lipid synthesis suppression, oxidative stress reduction and cognitive preservation.

Identifiers

Synonyms: CMS-121, CMS121, CMS 121
CAS No: 1353224-53-9
Formula / MW: C₂₀H₁₉N O₃ • ~321.37 g∙mol⁻¹
Primary targets: Acetyl‑CoA Carboxylase 1 (ACC1) and Fatty Acid Synthase (FASN) — key lipogenesis enzymes.

How It Works (Plain English)

CMS121 inhibits ACC1 and FASN, slowing the creation of new fatty acids inside cells and reducing the pool of lipids that can undergo harmful peroxidation.
This leads to less oxidative damage from lipid-peroxides, improved mitochondrial and cellular health, and a reduction in inflammatory/age-related stress signaling.
Because excess lipid synthesis and peroxidation are implicated in neuro-degeneration, metabolic disease and ageing, CMS121 is used to explore these mechanisms.

Why Researchers Use It

To investigate how reducing lipogenesis impacts memory decline, oxidative damage and lipid peroxidation in neurodegeneration models.
To explore metabolic and aging-related endpoints such as obesity, inflammation, insulin resistance and organ-damage markers.
To assess mitochondrial markers, lipidomics, and cellular resilience in translational ageing studies.

Key Studies — What Was Tested, What Changed, Why It Matters

Transgenic Alzheimer’s Model: Lipid Peroxidation & Cognition

What was tested: Mice (APPswe/PS1ΔE9) with Alzheimer-like pathology treated with CMS121 (~34 mg/kg/day for 3 months).
What changed: Cognitive performance restored to wild-type levels; lipid-peroxidation markers (4-HNE adducts) and 15-LOX2 levels reduced in hippocampus.
Why it matters: Demonstrates the link between lipid metabolism and neuro-degeneration and positions CMS121 as a tool for studying this axis.

Metabolic & Aging Models: Obesity, Liver + Kidney Protection

What was tested: Aged/diet-induced metabolic models treated with CMS121 (6 months diet containing CMS121) assessing weight gain, glucose/lipid parameters, liver/kidney.
What changed: ~40% less weight gain, improved glucose/lipid profiles, lowered hepatic inflammatory markers, improved kidney mitochondrial proteins.
Why it matters: Suggests lipogenesis inhibitors may protect peripheral organs and entire metabolic system, not just brain.

Potential Research Applications

Neurodegeneration & Ageing

Alzheimer’s-models, oxidative stress, lipid peroxidation, cognitive assays.

Metabolic & Obesity Research

Age-related obesity, insulin resistance, hepatic steatosis, kidney damage models.

Lipidomics & Mitochondrial Biology

Lipid-synthesis suppression, mitochondrial markers (TFAM, Nrf1), lipid peroxidation readouts.

Synergistic / Comparator Compounds

BAM15 (Mitochondrial Uncoupler)

Why pair: Combine lipogenesis inhibition (CMS121) with energy-expenditure activation (BAM15) for multi-axis metabolic read-out.

NMN (Nicotinamide Mononucleotide)

Why pair: Mitochondrial/NAD⁺ pathway + lipid metabolism modulation may produce layered bioenergetic outcomes.

SLU-PP-332 (Pan-ERR Agonist)

Why compare: Exercise-mimetic vs lipogenesis suppression—contrast different metabolic entry-points in obesity/aging studies.

Known Concerns (Context)

Pre-clinical tool compound: While CMS121 has entered Phase 1 (safety) studies, therapeutic use is not established—use in research context only.
Target breadth: Modulating ACC1/FASN affects multiple lipid pathways—off-target effects and compensatory metabolism may influence results.
Model specificity: Many positive findings are in ageing/AD or diet-induced models; translation to other tissues/systems may vary.
General: For laboratory research use only; not for human consumption or therapeutic use.

Specifications & Handling

Form: Small-molecule solid (lot-coded) — verify free base.
Storage: Dry, preferably ≤ −20 °C; protect from light and moisture.

In solution: Soluble in DMSO/ethanol; record solvent %, pH, time-to-assay; avoid multiple freeze-thaws.
Labeling: Tamper-evident; research-only; lot/SKU clearly displayed.

Regulatory & Use Notice

Sold for laboratory research use only. Not for human consumption, medical, or veterinary use. No human-use instructions are provided. Buyer is responsible for safe handling and regulatory compliance.