JAB-3312 is a potent, selective and allosteric SHP2 inhibitor with binding Kd of 0.37 nM and enzymatic IC50 of 1.9 nM.
JAB-3312 is inactive in inhibiting other 22 phosphatases (including SHP1 and the PTP domain of SHP2) and 25 kinases.
JAB-3312 exhibits IC50 of 7.4 nM in KYSE-520 antiproliferation assay, and IC50 of 0.23 nM in p-ERK inhibition assay in KYSE-520 cell line.
JAB-3312 (0.1-1 mg/kg, QD, p.o.) exhibited dose-dependent antitumor effects in KYSE-520 and MV-4–11 xenograft models.
