Migoprotafib (GDC-1971, RLY-1971) is a potent, selective, allosteric and orally bioavailable inhibitor of the non-receptor protein tyrosine phosphatase SHP2 (PTPN11), potently inhibits both wild-type SHP2 (IC50 <1 nM) and E76K activating mutant (IC50 < 250nM) in biochemical assays.
GDC-1971 inhibits cellular proliferation in models harboring receptor tyrosine kinases (RTKs), SHP2, NF1, KRAS, or BRAF mutations in a dose-dependent manner.
GDC-1971 potently inhibits the proliferation of cellular models harboring KRAS G12C or G12A mutations (median IC50 <80 nM) compared to models harboring other KRAS G12, G13 or Q61 mutations (median IC50 >1 uM).
GDC-1971 demonstrates dose-dependent RAS/MAPK pathway inhibition and induces significant tumor-growth inhibition in human xenograft models harboring EGFR and KRAS alterations.
GDC-1971 demonstrates increased suppression of the MAPK signaling cascade and anti-proliferation synergy when combining with EGFR, ALK, and KRAS G12C inhibitors in vitro.
GDC-1971 exhibits dramatic synergic anti-tumor growth effects in vivo, when combining with the KRAS G12C covalent inhibitor GDC-6036 (Cat# PC-73323).