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molecules of the month

“Compound (P)-14″

atropisomeric PI3K beta-selective inhibitor

off-target tox. in higher species, discontinued

from rational design of known starting point

J. Med. Chem., Apr. 15, 2020

Gilead Sciences, Seattle, WA + Foster

Compound (P)-14
1 min read

“Compound (P)-14″ is a PI3K beta-isoform selective lipid kinase inhibitor. While the compound is potent and has excellent oral PK in higher species, significant irreversible toxicity was observed in a tox. study, and the chemical series was discontinued. It’s always great when organizations disclose tox. findings to educate the community. Interestingly the molecule has a significant barrier to rotation around the benzimidazole ring and can be isolated as a stable atropisomer.


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