Abstract LB-057: 1-Benzylquinazoline-2,4(1H,3H)-diones as potent PARP inhibitors. SAR of the quinazoline group and in vivo efficacy of clinical candidate IMP4297

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.LB-057-LB-057
• Main Authors: Cai, Sui Xiong, Xu, Qingbing, Hu, Xiuhua, Jiang, Yangzhen, Wang, Guoxiang, Tian, Ed
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-LB-057

Poly (ADP-ribose) polymerase (PARP) is a critical enzyme for DNA repair and PARP-1 inhibitors have been found to be efficacious against cancers with BRCA mutations. Olaparib (AZD2281) has been approved as the first PARP-1 inhibitor for the treatment of ovarian cancers with BRCA mutations. In this presentation, we will report the SAR studies of 1-benzylquinazoline-2,4(1H,3H)-diones (BQD) as potent PARP inhibitors. We will present data for substituents at the quinazoline group of BQD, as well as in vivo efficacy data of IMP4297 which has been selected as clinical candidate for development. In a human triple negative breast cancer PDX model (BR-05-0028) with BRCA1 mutations, IMP4297 is highly efficacious against tumor growth with potency that is about 20-fold that of AZD2281. An IND for IMP4297 has been filed in China recently. Citation Format: Sui Xiong Cai, Qingbing Xu, Xiuhua Hu, Yangzhen Jiang, Guoxiang Wang, Ed Tian. 1-Benzylquinazoline-2,4(1H,3H)-diones as potent PARP inhibitors. SAR of the quinazoline group and in vivo efficacy of clinical candidate IMP4297. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-057.