CMS121

April 1, 2021

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.

CMS121 powder video

 

CMS121 powder Specifications

Product Name CMS121 powder
Chemical Name 4-(4-(Cyclopentyloxy)quinolin-2-yl)benzene-1,2-diol
Synonyms CMS-121

UNII-BW9P9F8JEY

BW9P9F8JEY

CMS 121

CAS Number 1353224-53-9
InChIKey OMHNVUCFPJJLKD-UHFFFAOYSA-N
SMILE C1CCC(C1)OC2=CC(=NC3=CC=CC=C32)C4=CC(=C(C=C4)O)O
Molecular Formula C20H19NO3
Molecular Weight 321.4 g/mol
Monoisotopic Mass 321.136493 g/mol
Melting Point N/A
Form powder
Solubility DMF: 30 mg/ml

DMSO: 20 mg/ml

Storage temp -20°C
Application CMS-121 has strong neuroprotective, anti-inflammatory, antioxidative and renoprotective activities. It has been used in Alzheimer’s disease research.

 

What is CMS121?

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.

 

What is CMS121 use for? CMS121 benefits

CMC121 improves memory and behavior

The results revealed that in both memory and behavior tests, mice with Alzheimer’s-like disease that received CMS121 treatment performed equally well as healthy control mice, while untreated mice with the disease performed poorly.

Not only that, but the brains of the treated mice showed differences at the cellular and molecular levels.

The researchers observed differences in the levels of lipids (fatty molecules that play key roles in cells throughout the body) in mice with the disease compared with both healthy mice and those treated with CMS121. Specifically, they discovered differences in lipid peroxidation, which leads to cell damage.

Mice that received CMC121 and healthy mice had lower levels of lipid peroxidation than mice with Alzheimer’s-like disease.

“That not only confirmed that lipid peroxidation is altered in Alzheimer’s, but that this drug is actually normalizing those changes,” explains the first author of the study, Dr. Gamze Ates.

 

CMS121 and Fisetin

The research materials here are of interest because fisetin has been shown to be a senolytic compound in mice, capable of selectively destroying harmful senescent cells. Other senolytics have reversed the progression of Alzheimer’s disease pathology in mouse models of the condition. Destroying senescent cells in the brain reduces inflammatory signaling, and chronic inflammation is a significant mechanism in neurodegenerative conditions such as Alzheimer’s disease. Whether this compound works well as a senolytic in humans has yet to be established – a clinical trial is underway, so hopefully we’ll find out in the next year or two.

The researchers here are not interested in cellular senescence at all, however, and instead base their work on the effects of fisetin and fisetin-like molecules on lipid metabolism in the brain. Back in 2014, they showed that fisetin slowed the onset of Alzheimer’s like symptoms in mice. The present work is much the same, except with an improved version of fisetin called CMS121. This all raises the question of whether their approach is working for the reasons that they think it is working.

 

CMS-121 and J-147

In mouse models of Alzheimer’s disease, the investigational drug candidates known as CMS121 and J147 improve memory and slow the degeneration of brain cells. Now, Salk researchers have shown how these compounds can also slow aging in healthy older mice, blocking the damage to brain cells that normally occurs during aging and restoring the levels of specific molecules to those seen in younger brains.

 

Reference

[1] 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.

[2] Geroprotective effects of Alzheimer’s disease drug candidates. Kepchia D, Currais A, Dargusch R, Finley K, Schubert D, Maher P.