BRD8833 is a small molecule that induces BCR-ABL Y253 phosphorylation disrupts BCR-ABL signaling pathway.
BRD8833 potently induces apoptosis of BCR-ABL-dependent cancer cells at a low nanomolar concentration.
BRD8833 shows potent cytotoxicity in K562 cells with EC50 of 69 nM.
BRD8833 dose-dependent cytotoxicity (EC50: 35-149 nM) for BCR-ABL positive CML cell lines (KCL22, BV-173, EM-2 and KYO-1), but not on HEK293T cells that lack BCR-ABL.
BRD8833 reduces the viability with an EC50 value of 280 nM in Ba/F3 cells expressing TEL-ABL, potently inhibits the viability of different oncogenic ABL-fusions.
BRD8833 exhibits high selectivity for CML cells dependent on ABL oncogenic fusions with minimal off-target effects on other cell lines.
BRD8833 is active in cells harboring a gatekeeper mutation (T315I), which renders active-site drugs (e.g., imatinib) ineffective, and in cells with other oncogenic ABL fusions (e.g., TEL-ABL) that are insensitive to approved drugs (e.g., asciminib).