Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 11, Issue 4, Pages 485-490Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.9b00611
Keywords
Apoptosis signal-regulating kinase 1; ASK1; rational design; CNS penetration; neurodegenerative diseases
Categories
Ask authors/readers for more resources
Apoptosis signal-regulating kinase 1 (ASK1) is a key mediator in the apoptotic and inflammatory cellular stress response. To investigate the therapeutic value of modulating this pathway in neurological disease, we have completed medicinal chemistry studies to identify novel CNS-penetrant ASK1 inhibitors starting from peripherally restricted compounds reported in the literature. This effort led to the discovery of 21, a novel ASK1 inhibitor with good potency (cell IC50 = 138 nM), low clearance (rat Cl/Cl-u = 0.36/6.7 L h(-1) kg(-1)) and good CNS penetration (rat K-p,K- uu = 0.38).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available