产品描述:
LDC000067 is a cyclin-dependent kinase 9 (Cdk9) inhibitor (IC50 = 44 nM).{46601} It is selective for Cdk9 over Cdk1, -2, -4, -6, and -7 (IC50s = 5.5, 2.44, 9.24, >10, and >10 μM, respectively), as well as a panel of 28 additional kinases at 10 μM. LDC000067 (10 μM) inhibits transcription dependent on the Cdk9-cyclin T complex positive transcription elongation factor b (P-TEFb) in vitro and de novo RNA synthesis in A549 cells. It induces apoptosis in A549 and MCF-7 cancer cells. LDC000067 prevents IL-1β-induced production of matrix metalloproteinase-3 (MMP-3), MMP-9, MMP-13, IL-6, IL-8, and TNF-α and NF-κB activation in SW 1353 chondrocytes.{46602} In vivo, LDC000067 (7.5 mg/kg) delays cartilage degeneration in a mouse model of anterior cruciate ligament transection (ACLT). It also prevents bone resorption in mouse models of ACLT- or LPS-induced osteoarthritis.{46603}