Pyrotinib

Pyrotinib (SHR-1258) is a potent and selective EGFR/HER2 dual inhibitor with IC₅₀s of 13 and 38 nM, respectively^[1]. IC50 & Target: IC50: 13 nM (EGFR), 38 nM (HER2)^[1] In Vitro: Pyrotinib has high potency in HER2-dependent cell lines (BT474, SK-OV-3), while showing much weaker inhibition in the HER2 negative cell line (MDA-MB-231). It inhibits BT474 and SK-OV-3Pyrotinib cells with IC₅₀s of 5.1 and 43 nM, respectively. Pyrotinib displays high selectivity as HKI-272 when tested in a panel of different kinases such as KDR, c-Kit, PDGFRβ, c-Src and C-Met (c-Src with an IC₅₀ of 790 nM, and others over 3000 nM)^[1]. In Vivo: Pyrotinib has acceptable bioavailability of 20.6%, 43.5% and 13.5% in nude mice, rats and dogs, respectively. Pyrotinib has favorable drug-like physicochemical properties and shows relatively higher oral exposure in human subjects with a much longer half life than that of preclinical animal species such as mouse, rat and dog. The TGI % (tumor growth inhibition) of Pyrotinib on day 21 is 109%, 157%, 159% at the doses of 5 mg/kg, 10 mg/kg, 20 mg/kg respectively. Pyrotinib in SK-OV-3 ovarian xenograft model shows TGI% on day 21 of 2%, 12%, 83% at the doses of 2.5 mg/kg, 5 mg/kg, 10 mg/kg respectively), which further confirms its robust in vivo antitumor efficacy at 10 mg/kg^[1].