CMS121

CMS-121 is a quinolone derivative and an orally active acetyl-CoA carboxylase 1 (ACC1) inhibitor. CMS-121 protects HT22 cells against ischemia and oxidative damage with EC50 values of 7 nM and 200 nM, respectively. CMS-121 has strong neuroprotective, anti-inflammatory, antioxidative and renoprotective activities[1][2][3].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Metabolic Enzyme/Protease >> Acetyl-CoA Carboxylase

Research Areas >> Neurological Disease

Acetyl-CoA carboxylase 1 (ACC1)[1]

CMS-121 (1 µM; 4 hours; HT22 cells) treatment increases the phosphorylation of ACC1 at serine 79. CMS-121 can increase acetyl-CoA in cells[1]. Western Blot Analysis[1] Cell Line: HT22 cells Concentration: 1 µM Incubation Time: 4 hours Result: Increases the phosphorylation of ACC1 at serine 79.

CMS-121 (~20 mg/kg; oral administration; daily; for 4 months; female SAMP8 mice) treatment reduces cognitive decline as well as metabolic and transcriptional markers of aging in the brain when administered to rapidly aging SAMP8 mice. CMS-121 preserves mitochondrial homeostasis by regulating acetyl-coenzyme A (acetyl-CoA) metabolism[1]. Animal Model: Female SAMP8 mice (9 months old)[1] Dosage: ~20 mg/kg/day Administration: Oral administration; daily; for 4 months Result: Reduced cognitive decline as well as metabolic and transcriptional markers of aging in the brain.

[1]. Currais A, et al. Elevating acetyl-CoA levels reduces aspects of brain aging. Elife. 2019 Nov 19;8. pii: e47866.

[2]. Chiruta C, et al. Chemical modification of the multitarget neuroprotective compound fisetin. J Med Chem. 2012 Jan 12;55(1):378-89.

[3]. Prior M, et al. Back to the future with phenotypic screening. ACS Chem Neurosci. 2014 Jul 16;5(7):503-13.