BSM-1516

BSM-1516 is a **novel, potent, and selective small molecule inhibitor of Flap endonuclease 1 (FEN1)**, developed by Blacksmith Medicines. FEN1 is a structure-specific metallonuclease critical for DNA replication and repair, and is frequently overexpressed in cancer. BSM-1516 exhibits high selectivity for FEN1 (IC50 = 7 nM), being ~65-fold more potent against FEN1 than against the related enzyme Exonuclease 1. Its mechanism exploits synthetic lethality in **homologous recombination (HR)-deficient cancers** (e.g., BRCA2-deficient cells), leading to cell cycle arrest and DNA damage accumulation selectively in tumor models with defective HR. BSM-1516 synergizes in vitro with inhibitors of USP1, PARP, PARG, and ATR, making it a strong candidate for combination treatments targeting DNA damage response (DDR) pathways. Preclinical studies demonstrate oral bioavailability, favorable pharmacokinetics, and a good safety profile. Development remains preclinical, with ongoing evaluation as both monotherapy and in combination regimens for cancer[1][2][3][5][9][11][13][14][15].

Other names

Blacksmith Medicines FEN1 inhibitorFEN1 inhibitorFEN-1 inhibitorFEN 1 inhibitorBlacksmith Medicines FEN1 program