AG-14361

AG-14361 is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1, Ki = 6.3 nM for the human enzyme). It inhibits PARP1 activity in permeabilized and intact SW620 cells (IC50s = 29 and 14 nM, respectively). AG-14361 (0.4 µM) potentiates the growth inhibitory effects of temozolomide (Cay-14163) in HCT116, A2480, and CP70 cells and of the topoisomerase I inhibitor topotecan (Cay-14129) by greater than three-fold in PARP1+/+ primary embryonic fibroblasts. It slows the rejoining of camptothecin-induced DNA strand breaks. AG-14361 also inhibits cell growth in a PARP1-independent manner with GI50 values of 66 and 65 µM, respectively, in cell lines derived from PARP1+/+ and PARP1-/- mice. AG-14361 (15 mg/kg), in combination with temozolomide, leads to tumor regression in an SW620 mouse xenograft model.Formal Name: 2-[4-[(dimethylamino)methyl]phenyl]-5,6-dihydro-imidazo[4,5,1-jk][1,4]benzodiazepin-7(4H)-one. CAS Number: 328543-09-5. Molecular Formula: C19H20N4O. Formula Weight: 320.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 20 mg/ml, Ethanol: 2 mg/ml, PBS (pH 7.2): 0.2 mg/ml. lambdamax: 210, 240, 312 nm. SMILES: O=C1NCCN2C3=C1C=CC=C3N=C2C4=CC=C(CN(C)C)C=C4. InChi Code: InChI=1S/C19H20N4O/c1-22(2)12-13-6-8-14(9-7-13)18-21-16-5-3-4-15-17(16)23(18)11-10-20-19(15)24/h3-9H,10-12H2,1-2H3,(H,20,24). InChi Key: SEKJSSBJKFLZIT-UHFFFAOYSA-N.