BRD-K98645985

Overview

BRD-K98645985 is a recently described tool compound targeting the ARID1A-containing BAF (SWI/SNF) chromatin-remodeling complex. It has demonstrated potent single-agent antitumor activity in SCLC preclinical models and Bliss synergy with the BET bromodomain inhibitor JQ1. Clinical pharmacology data and off-target effects in human tissues remain to be characterized.

Evidence in the corpus

• BRD-K98645985 shows potent single-agent antitumor activity in SCLC xenograft models PMID:22037554.
• Bliss synergy with jq1 in vitro and in vivo; combination achieves superior tumor suppression versus either agent alone (p < 0.0001) in DMS273 and H446 SCLC xenograft models PMID:22037554.
• The combination targets ARID1A-deficient SCLC through a synthetic lethality approach: BRD-K98645985 disrupts the BAF complex while JQ1 blocks BRD4-driven transcription PMID:22037554.

Resistance mechanisms

Cancer types (linked)

• SCLC

Sources

• PMID:22037554

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