CC-486 and Venetoclax for Acute Myeloid Leukemia

Venetoclax is a potent, selective and orally bioavailable small molecule inhibitor of BCL-2 that binds with \> 1,000-fold higher affinity to BCL-2 (Ki \< 0.010 nM) than other apoptotic pathway proteins BCL-XL (Ki = 48 nm) or MCL-1 (Ki \> 444 nM). Leukemia stem cells (LSCs) overexpress BCL-2, and BCL-2 overexpression has been associated with worse outcomes in AML.

An oral formulation of azacitidine currently being developed for the treatment of hematological and solid malignancies.