Figure 2
From: K-Map: connecting kinases with therapeutics for drug repurposing and development
Query results for MET using K d database. These four compounds were returned withconnectivity score >0.9, indicating that these compounds were highly specificin inhibiting MET. SGX-523 is ranked #1 and is a specific METinhibitor, with Kd = 0.0019 μM as illustrated in the kinasefamily tree. PHA-665752 is ranked #2 with Kd = 0.0027 μMagainst MET. These two compounds (SGX-523 and PHA-665752) werepreclinical compounds and have not moved into clinical trials. Forentinib is anFDA-approved drug that inhibits MET and KDR (Kd =0.014 μM against MET) and is ranked #3; however, the pvalue is high (p = 0.801). Crizotinib is also an FDA-approved drugthat inhibits ALK, and this compound has Kd = 0.021 μMagainst MET (p value = 0.004). Crizotinib was validated inin vitro experiments and showed synergistic effects when combinedwith Nutlin-3 in p53wild-type cancer cell lines [13].