NMS-P118 is a potent, orally available, and highly selective PARP-1 Inhibitor for cancer therapy. IC50 & Target: IC50: 0.04 μM (PARP-1, HeLa Cell)^[1]
KD: 0.009 μM (PARP-1)^[1] In Vitro: NMS-P118 is found to be less myelotoxic in vitro than olaparib (now marketed as Lynparza), a dual PARP-1/-2 inhibitor. NMS-P118 proves to be metabolically stable, it modestly inhibites two cytochrome P450 family members (CYP-2B6 IC₅₀: 8.15 μM; CYP-2D6 IC₅₀: 9.51 μM) out of eight isoforms tested. Its ability in hampering the proliferation of bone marrow cells is from 5 to > 60 times lower then olaparib according to the species^[1]. In Vivo: NMS-P118 is a potent (K_D=0.009 μM) PARP-1 inhibitor, showing 150-fold selectivity over PARP-2 (K_D=1.39 μM). NMS-P118 possesses excellent pharmacokinetic profile and nearly complete oral bioavailability both in mice and rats. It proved to be highly efficacious in vivo both as single agent in MDA-MB-436 human breast cancer tumors and in combination with temozolomide in CAPAN-1 human pancreatic tumors growing as xenografts in the mouse. The compound is well tolerated at highly efficacious doses and is endowed with an excellent ADME profile^[1].