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molecules of the month

A-1331852

first-in-class, bioavailable BCL-XL inhibitor

oral efficacy in xenograft, led to ADC dev.

from SBDD of prior BH3 mimetics

ACS Med. Chem. Lett., Jul. 5, 2020

AbbVie, North Chicago, IL / Genentech

A-1331852
1 min read

A-1331852 is a highly potent, orally bioavailable inhibitor of BCL-XL, blocking a protein-protein interaction resulting in tumor cell apoptosis. The compound was an important tool compound for understanding the biology of BCL-family protein inhibitors (particularly around heme toxicities), and ultimately led to the development of an antibody-drug conjugate (ABBV-155) which recently entered Ph. I studies for solid tumors. Andrew Judd gave a great presentation on the BCL-XL story at last year’s Bay Area Chemistry Symposium highlighting this project, and I’m looking forward to seeing the ADC part of the story being published in the future.


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