Biochem/physiol Actions
Potent ATP site-targeting kinase inhibitor against aurora A/B/C, FGFR1, Abl, Ret, and TrkA with anti-cancer efficacy in cultures and in vivo.
Danusertib (PHA-739358) is a potent ATP site-targeting aurora kinase inhibitor (IC50 = 13 nM/A, 79 nM/B, 61 nM/C; [ATP] = 2 Km, [substrate] = 5 Km) with additional potency against FGFR1, Abl, Ret, and TrkA (IC50 = 47, 25, 31, 31 nM, respectively; [ATP] = 2 Km, [substrate] = 5 Km). Danusertib exhibits antiproliferation activity in cancer cultures (IC50 20-300 nM among 15 cancer cell lines) and antitumor efficacy in mice with human cancer xenografts in vivo via i.v. (30 mg/kg q.d. or b.i.d.) or i.p. (15 mg/kg b.i.d.).