Biochem/physiol Actions

BAY-958 (LDC526) is an orally active, ATP site-targeting, potent and selective PTEFb/CDK9 inhibitor (hCDK9-CycT1 IC50 = 5-11 nM; [ATP] = 10 µM) with 52- to >2000-fold selectivity over CDK1-7 with antiproliferative activity in cancer cultures (IC50 = 0.28 µM/96h/MOLM-13, 1 µM/96h/HeLa, 0.55 µM/48h/MEC-1, 0.28 µM/48h/CCL patient PBMCs). When administered orally in mice, BAY-958 significantly suppresses MOLM-13 acute myeloid leukemia (AML) tumor growth in mice (30/40 mg/kg/day p.o.; HCl salt) and exhibits in vivo efficacy in two murine chronic lymphocytic leukemia (CLL) models (50 & 70 mg/kg/day p.o.; free base).