molecules of the year


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

1 min read

July’s molecule, the AbbVie BCL-XL inhibitor A-1331852, is a highly potent, orally bioavailable, protein-protein interaction inhibitor which triggers tumor cell apoptosis. The molecule emerged from a long, challenging fragment-assisted discovery campaign, as might be expected for a formerly “undruggable” target. The compound was an important tool compound for understanding the on-target biology of BCL-family protein inhibitors (particularly with respect to heme toxicities), and ultimately led to the development of a safer antibody-drug conjugate (ABBV-155) which recently entered Ph. I studies for solid tumors. Impressively, it was the AbbVie chemistry team that pushed to successfully continue the BCL-XL program with a biologic modality.

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