CMS-121

CMS-121

CMS-121 is a synthetic quinoline derivative developed at the Salk Institute (Schubert laboratory) from a medicinal chemistry series derived from the naturally occurring flavonoid fisetin. During its molecular optimization, the parent compound’s chromone core was strategically replaced with a quinoline scaffold while preserving the critical catechol (benzene-1,2-diol) pharmacophore. This modification means the molecule is functionally fisetin-derived rather than structurally fisetin-shaped. Primarily investigated for its neuroprotective and lipid-regulating properties, CMS-121 serves as a high-precision reference standard for evaluating fatty acid synthesis pathway kinetics, lipid peroxidation mechanisms, and cellular defense models under oxidative stress.

Technical Specifications

Research Applications & Mechanism of Interest

Unlike simple direct-acting antioxidants, CMS-121 exerts its biological effects through a highly specific transcriptional and enzymatic pathway. Identified initially through phenotypic screening and later validated by molecular target mapping, its activity relies on the targeted modulation of lipid biosynthesis.

Primary fields of investigative laboratory research include:

• FASN Target-Engagement Assays: Investigating the compound’s role as a partial inhibitor of fatty acid synthase (FASN)—the multi-enzyme complex responsible for synthesizing palmitate from acetyl-CoA and malonyl-CoA.

• Mitigation of Lipid Peroxidation: Tracking downstream pathways where partial FASN inhibition limits the intracellular pool of newly synthesized fatty acids. Because fewer fresh lipids are available for oxidation, this cascade helps isolate the mechanisms of cellular protection from direct radical scavenging.

• Oxytosis and Ferroptosis Modeling: Utilizing HT22 or primary neuronal culture lines to analyze cellular survival thresholds under severe oxidative stress, glutamate-induced cell death, or ferroptotic stress.

• Comparative Derivative Profiling: Serving as an active benchmark reference alongside native fisetin and other synthetic Salk Institute analogues (such as J-147) to establish structure-activity relationships (SAR) for substituted quinoline frameworks.

Analytical Advisory: CMS-121 is classified specifically as an inhibitor of an anabolic enzyme (FASN). It is not a metabolic activator, and experimental models should be calibrated to monitor metabolic inhibition rather than upregulation.

Storage & Handling Guidelines

To maintain molecular configuration, prevent oxidation of the catechol group, and secure reproducible analytical assays:

• Thermal Controls: Maintain long-term preservation in a deeply frozen state at -20°C. Working stocks can be held under refrigeration at 2–8°C for short intervals.

• Moisture Protection: Keep the container tightly sealed inside a desiccated environment after each use to prevent atmospheric degradation.

• Photolytic Isolation: Catechol-containing compounds are highly sensitive to light-induced oxidation. Store and handle the compound strictly within opaque or high-grade amber laboratory containment vessels.

• Quality Assurance Auditing: Kimera Chems subjects every production batch to a strict dual-method verification protocol combining High-Performance Liquid Chromatography (HPLC) and CHN elemental analysis to independently audit compound identity, molecular mass, and absolute purity baselines.

Research Use Only Disclaimer: This product is engineered, synthesized, and distributed strictly as a Research Use Only (RUO) laboratory reference chemical. It is not an FDA-approved drug, licensed medication, active pharmaceutical ingredient, or dietary supplement, and is strictly prohibited for human or veterinary consumption. Kimera Chems supplies these reference standards exclusively to accredited institutional laboratories and certified scientific investigators for in vitro analytical research.

Frequently Asked Research Questions

Why is CMS-121 described as “fisetin-derived but not fisetin-shaped”?

During medicinal optimization, chemists at the Salk Institute completely swapped the core heterocyclic chromone ring system of fisetin with a quinoline ring system while keeping the active catechol group intact. This change drastically improves the compound’s pharmacokinetics and target selectivity without relying on the structural footprint of the original flavonoid.

Does CMS-121 act as a direct antioxidant?

No. Published target validation indicates that its protective effect in cellular models runs downstream of enzyme inhibition. By partially blocking FASN, it suppresses the synthesis of fatty acids that would otherwise undergo lipid peroxidation under oxidative stress. The preservation of cellular integrity is a consequence of this pathway block rather than direct radical-scavenging activity.

Scientific References

1. Chiruta, C., et al. (2012). “Chemical modification of the multitarget neuroprotective compound fisetin.” Journal of Medicinal Chemistry, 55(1), 378–389. DOI: 10.1021/jm2012563.

2. Ates, G., et al. (2020). “CMS121, a fatty acid synthase inhibitor, protects against excess lipid peroxidation and inflammation.” Redox Biology, 36, 101648. DOI: 10.1016/j.redox.2020.101648.