Pamiparib

Pamiparib is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 (IC50s = 1.3 and 0.92 nM, respectively). It is selective for PARP1 and PARP2 over PARP3 (IC50 = 0.068 µM) and other PARP isoforms (IC50s = 2.4->100 µM), as well as over tankyrase 1 (TNKS1) and TNKS2 (IC50s = 0.23 and 0.14 µM, respectively). Pamiparib inhibits PARP activity induced by hydrogen peroxide in HeLa cells with an IC50 value of 0.24 nM. It selectively inhibits proliferation of MDA-MB-436 cells expressing mutant BRCA1 and Capan-1 cells expressing mutant BRCA2 (EC50s = 41 and 960 nM, respectively) over MDA-MB-231 cells expressing wild-type BRCA (EC50 = ~9,000 nM). Pamiparib (1.6-6.3 mg/kg twice per day) induces tumor regression in an MDA-MB-436 mouse xenograft model. It also potentiates increases in survival induced by temozolomide (Cay-14163) in an H209 mouse xenograft model of small cell lung cancer brain metastasis.Formal Name: (10aR)-2-fluoro-5,8,9,10,10a,11-hexahydro-10a-methyl-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one. CAS Number: 1446261-44-4. Synonyms: BGB-290. Molecular Formula: C16H15FN4O. Formula Weight: 298.3. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 20 mg/ml, DMF:PBS (pH 7.2) (1:10): 0.09 mg/ml, DMSO: 1 mg/ml. lambdamax: 225, 262, 297 nm. SMILES: C[C@@]12C3=C4C5=C(C(NN=C4CN1CCC2)=O)C=C(F)C=C5N3. InChi Code: InChI=1S/C16H15FN4O/c1-16-3-2-4-21(16)7-11-13-12-9(15(22)20-19-11)5-8(17)6-10(12)18-14(13)16/h5-6,18H,2-4,7H2,1H3,(H,20,22)/t16-/m1/s1. InChi Key: DENYZIUJOTUUNY-MRXNPFEDSA-N.