DSB2455

DSB2455 is a next-generation, highly selective small molecule inhibitor of poly(ADP-ribose) polymerase 1 (PARP1), developed by Duke Street Bio for the treatment of solid tumors, particularly those harboring homologous recombination deficiencies (HRD) such as BRCA mutations. Unlike first-generation non-selective PARP inhibitors that target both PARP1 and PARP2 and are limited by safety concerns—especially in combination with chemotherapy or radiotherapy—DSB2455 is designed to selectively inhibit only PARP1. This selectivity aims to provide an improved therapeutic index, enhanced efficacy, and better tolerability. Notably, DSB2455 demonstrates central nervous system (CNS) penetrance, making it suitable for treating brain metastases from cancers like triple-negative breast cancer with BRCA or HRR alterations. The drug has shown compelling preclinical efficacy and safety data and has received FDA Fast Track designation for brain metastases from triple-negative breast cancer[3][2][6][10].

Other names

PARP1 inhibitor (Duke Street Bio)