ABT-199(GDC-0199) is aBcl-2-selective inhibitor withKiof<0.01 nM,>4800-fold more selective versus Bcl-xL and Bcl-w,and no activity to Mcl-1.Phase 2.
生化机理
ABT-199 is a potent and selective inhibitor of B-cell lymphoma-2(BCL-2) family proteins,currently in clinical trials.ABT-199 inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets.A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24h.These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.