Therapeutics: c-Met proto-oncogene (MET; HGFR)

In vitro and mouse studies have identified a 1-sulfonyl-pyrazolo[4,3-b]pyridine-based MET inhibitor that could help treat various cancers. Chemical synthesis and in vitro testing of 1-sulfonyl-pyrazolo[4,3-b]pyridine analogs identified a lead compound that inhibited MET at an IC50 value of ~0.6 nM whereas it inhibited 19 other kinases at IC50 values of more than 1,000 nM. In a panel of four MET-driven cancer cell lines, the compound inhibited growth at IC50 values of 0.27-1.15 nM. In a mouse xenograft model of lung cancer, a 50 mg/kg oral dose of the lead compound decreased tumor growth with potency comparable to an equivalent oral dose of Xalkori crizotinib. Next steps could include evaluating the safety of the lead MET inhibitor in other models of cancer...