Pyrotinib dimaleate (SHR-1258 dimaleate) is a potent and selective dual inhibitor of EGFR/HER2 with IC50s of 13 and 38 nM, respectively.

Pyrotinib dimaleate exhibits potent activity in HER2-positive cell lines (BT474, SK-OV-3), yet demonstrates significantly diminished inhibitory effects on the HER2-negative cell line (MDA-MB-231). Furthermore, it shows a high degree of selectivity, akin to HKI-272, across a range of kinases including KDR, c-Kit, PDGFRβ, c-Src, and C-Met, specifically displaying an IC50 of 790 nM for c-Src and over 3000 nM for the others. Notably, it achieves inhibition of BT474 and SK-OV-3 cells with IC50 values of 5.1 and 43 nM, respectively.

Pyrotinib dimaleate has favorable drug-like physicochemical properties and shows relatively higher oral exposure in human subjects (oral; t1/2=15 h) with a much longer half-life than that of preclinical animal species such as mice (i.v.; t1/2=1.56 h; i.g.; t1/2=2.52 h) and rat (i.v.; t1/2=4.42 h; i.g.; t1/2=3.38 h). Pyrotinib dimaleate has acceptable bioavailability of 20.6%, 43.5%, and 13.5% in nude mice, rats, and dogs, respectively.