fbpx

molecules of the month

“compound 38a”

orally active ChemR23 GPCR inhibitor

oral effects on dendritic cells in higher species

from cell-based screen and optimization

Bioorg. Med. Chem., Jul. 14, 2020

Kyowa Kirin, Shizuoka, JP

Structure of compound 38a
1 min read

“compound 38a” is an inhibitor of ChemR23, a chemokine-receptor-like GPCR with a role in plasmacytoid dendritic cell (pDC) trafficking. The ChemR23 inhibitor was developed with the intention of suppressing the migration of pDCs, which may be useful in certain autoimmune diseases. A key change that dramatically improved bioavailability was swapping a tetrazole with the 1,2,4-oxadiazol-5-one ring. The 1,2,4-oxadiazol-5-one is often proposed as a carboxylic acid isostere but I was surprised to see such a dramatic effect on bioavailability. It’s also surprising that the final compound, which bears two negatively charged groups (acid + oxadizolone) has significant oral exposure in monkeys.


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: