KIT/PDGFRA-IN-2

KIT/PDGFRA-IN-2 is a highly potent and selective inhibitor that achieves sub-nanomolar activity against PDGFRA-D842V and 37 nM activity against the PDGFRA-G680R solvent-front mutant^[1].
KIT/PDGFRA-IN-2 (2-3-fold molar excess; 3 h) adopts a preorganized optimal binding conformation that fits well within the ATP-binding pocket of PDGFRA^G680R without the need for significant structural rearrangement of either the inhibitor or the mutant kinase^[1].
KIT/PDGFRA-IN-2 (5 µM; 20 h) displays a highly improved phenotypic selectivity profile relative to Avapritinib in non-target U2OS cells, inducing minimal off-target cellular morphological perturbations that predict reduced likelihood of undesired systemic toxicity^[1].
KIT/PDGFRA-IN-2 (compound 45) (8 distinct concentrations across the test range) exerts potent growth inhibitory activity in PDGFRA-D842V mutant GIST cells at 10 nM, and is the most effective reported inhibitor against the Avapritinib (HY-101561)-resistant PDGFRA-D842V/G680R double mutant, achieving sub-micromolar GR₅₀ values below 1000 nM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.