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Selective Inhibition of the Second Bromodomain of BET Family Maintains Anti-Tumor Efficacy and Improves Tolerability

ABSTRACT: Here we report the discovery of ABBV-744, a first in class, highly potent and selective inhibitor of BET family BD2 domains with drug like properties. ChIP-seq analysis revealed that ABBV-744 displaced BRD4 from AR-containing super enhancers and elicited potent inhibition of AR-dependent transcription without causing broad transcription alterations associated with exposure to pan BET inhibitors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118247 | GEO | 2020/01/22

REPOSITORIES: GEO

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Selective Inhibition of the Second Bromodomain of BET Family Maintains Anti-Tumor Efficacy and Improves Tolerability (LNCaP RNA-seq)

Project description:Here we report the discovery of ABBV-744, a first in class, highly potent and selective inhibitor of BET family BD2 domains with drug like properties. RNA-seq analysis revealed that ABBV-744 elicited potent inhibition of AR-dependent transcription without causing broad transcription alterations associated with exposure to pan BET inhibitors.

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Selective inhibition of the second bromodomain of BET family proteins results in robust antitumor activity in preclinical models of acute myeloid leukemia

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