fbpx

molecules of the month

compound 25

kinome selective, CNS-penetrant, type I LRRK2 inhibitor

in vivo activity in preclinical PK/PD model

scaffold hopping + opt. of MLi-2

J. Med. Chem., December 7, 2022

Merck & Co., Boston, MA & Kenilworth, NJ

compound 25 chemical structure kinome selective, CNS-penetrant, type I LRRK2 inhibitor - Merck & Co., Boston, MA & Kenilworth, NJ
4 mins read

What is it? “Compound 25” is a selective, CNS-penetrant, ATP-competitive LRRK2 inhibitor that entered preclinical candidate enabling studies but was discontinued for undisclosed reasons. The molecule possesses two interesting chemical features: a “bow-tie” spirocyclopropyl group that made a significant impact on potency and overall properties, and a non-classical C-H hinge binder. The molecule was nominated by reviewer Dennis Koester, who says: “Although they terminated the compound for undisclosed but scientific reasons, I think it is a wonderful drug discovery story. Of note for a CNS target, they only looked at BCRP late in the program and discovered the compound to be a BCRP substrate and inhibitor leading to a low Kpu,u in NHPs compared to rats. The compound was not…


request a trial

You don’t have time to read everything, but you can’t afford to fall behind.

Drug Hunter Premium is drug discovery, distilled, so you can quickly catch up and make informed decisions based on industry examples.

Get ahead now by requesting a trial.


already a member? log in: