Oritinib (SH-1028) is an inhibitor of EGFR with IC50s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM for EGFR (wt), EGFR (L858R), EGFR (L861Q), EGFR (L858R/T790M), EGFR (d746-750), EGFR (d746-750/T790M), respectively. Oritinib can be used in studies about the treatment of non-small cell lung cancer.

EGFR (d746-750/T790M):0.89 nM, EGFR (L861Q):4 nM, EGFR (WT):18 nM, EGFR (d746-750):1.4 nM, EGFR L858R/T790M:0.1 nM, EGFR L858R:0.7 nM

Oritinib (0.001, 0.01, 0.1, 1, and 10 μM) selectively inhibits EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC50s of 3.932, 9.39 and 7.63 nM, respectively. Oritinib (0.1 μM) continuously inhibits the phosphorylation of EGFR in PC-9 and NCI-H1975 cells[1].

In female mice bearing NCI-H1975 and A431 xenograft models， Oritinib (2.5, 5, and 15 mg/kg; oral) significantly inhibits proliferation of tumor cells with no TKI-induced weight loss. In NCI-H1975 tumor-bearing mice, Oritinib (2.5, 5, and 15 mg/kg; oral) shows good bioavailability(Tmax = 1.5-2 h) and extensive distribution from the plasma to the tissues. The AUC0–t values in plasma are 118, 300 and 931 ng×h/mL on Day 1, while 272, 308 and 993 ng×h/ml on Day 14, respectively[1].