Venetoclax

Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a K_i of less than 0.01 nM. Venetoclax induces autophagy^[1][2][3]. IC50 & Target:Ki: <0.01 nM (Bcl-2), 48 nM (Bcl-xl), 245 nM (Bcl-w), >444 nM (Mcl-1)^[1] In Vitro: Venetoclax (ABT-199) potently kills FL5.12-BCL-2 cells (EC₅₀=4 nM), Venetoclax (ABT-199) shows much weaker activity against FL5.12-BCL-XL cells (EC₅₀=261 nM). ABT-199 also shows selectivity in cellular mammalian two-hybrid assays, where it disrupts BCL-2-BIM complexes (EC₅₀=3 nM) but is much less effective against BCL-XL-BCL-XS (EC₅₀=2.2 μM) or MCL-1-NOXA complexes^[1]. In Vivo: After a single oral dose of 12.5 mg per kg body weight in xenografts derived from RS4;11 cells (ALL), Venetoclax (ABT-199) causes a maximal tumor growth inhibition (TGI_max) of 47% (P<0.001) and tumor growth delay (TGD) of 26% (P<0.05)^[1].
Treatment of established xenografted (a mouse xenograft model of the T-ALL cell line LOUCY) tumors with Venetoclax (ABT-199) 100 mg/kg for 4 days results in a significant reduction of leukemic burden^[2].