For research use only. Not for therapeutic Use.
A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with Ki of 1 nM and 1.5 nM, respectively.
A-966492 is one of the most potent PARP inhibitors. A-966492 displays excellent potency against the PARP-1 enzyme with a Ki of 1 nM and an EC50 of 1 nM in a whole cell assay. A-966492 significantly enhances the efficacy of TMZ in a dose-dependent manner. In addition, A-966492 is orally bioavailable across multiple species, crosses the blood−brain barrier, and appears to distribute into tumor tissue. A-966492 represents a promising, structurally diverse benzimidazole analogue and is being further characterized preclinically[1].
A-966492 demonstrates good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin. In addition, A-966492 has excellent pharmaceutical properties and has demonstrated in vivo efficacy in preclinical mouse tumor models in combination with TMZ and carboplatin, as well as single agent activity in a BRCA1-deficient MX-1 tumor model. A-966492 is further characterized in Sprague−Dawley rats, beagle dogs, and cynomolgus monkeys, with A-966492 demonstrating oral bioavailabilities of 34−72% and half-lives of 1.7−1.9 hours. In vivo, A-966492 demonstrates significant enhancement of the efficacy of TMZ in a murine B16F10 syngeneic melanoma model, with the A-966492 combination groups showing superior efficacy[1].
| Catalog Number | I005541 |
| CAS Number | 934162-61-5 |
| Synonyms | 2-[2-fluoro-4-[(2S)-pyrrolidin-2-yl]phenyl]-1H-benzimidazole-4-carboxamide |
| Molecular Formula | C18H17FN4O |
| Purity | ≥95% |
| InChI | InChI=1S/C18H17FN4O/c19-13-9-10(14-5-2-8-21-14)6-7-11(13)18-22-15-4-1-3-12(17(20)24)16(15)23-18/h1,3-4,6-7,9,14,21H,2,5,8H2,(H2,20,24)(H,22,23)/t14-/m0/s1 |
| InChIKey | AHIVQGOUBLVTCB-AWEZNQCLSA-N |
| SMILES | C1CC(NC1)C2=CC(=C(C=C2)C3=NC4=C(C=CC=C4N3)C(=O)N)F |
| Reference | [1]. Penning TD, et al. Optimization of phenyl-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious |
