LDC000067

LDC000067 is a cyclin-dependent kinase 9 (Cdk9) inhibitor (IC50 = 44 nM). 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-1beta-induced production of matrix metalloproteinase-3 (MMP-3), MMP-9, MMP-13, IL-6, IL-8, and TNF-alpha and NF-kappaB activation in SW 1353 chondrocytes. 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.Formal Name: 3-[[6-(2-methoxyphenyl)-4-pyrimidinyl]amino]-benzenemethanesulfonamide. CAS Number: 1073485-20-7. Synonyms: LDC067. Molecular Formula: C18H18N4O3S. Formula Weight: 370.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 2 mg/ml. lambdamax: 213, 265, 302 nm. SMILES: COC1=CC=CC=C1C2=NC=NC(NC3=CC(CS(N)(=O)=O)=CC=C3)=C2. InChi Code: InChI=1S/C18H18N4O3S/c1-25-17-8-3-2-7-15(17)16-10-18(21-12-20-16)22-14-6-4-5-13(9-14)11-26(19,23)24/h2-10,12H,11H2,1H3,(H2,19,23,24)(H,20,21,22). InChi Key: GGQCIOOSELPMBB-UHFFFAOYSA-N.