Overview
Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) designed to effectively target ROS1 and TRK A/B/C, with the potential to treat TKI-naïve or -pretreated patients. In July 2020, Zai Lab obtained exclusive rights to develop and commercialize repotrectinib in greater China from Turning Point Therapeutics.
Mechanism of Action
Repotrectinib is a low-molecular-weight macrocyclic tyrosine kinase inhibitor of ROS1, TRK, and ALK. Repotrectinib was designed to efficiently bind with the active kinase conformation and avoid steric interference from a variety of clinically resistant mutations. The compact and rigid three-dimensional structure enables repotrectinib to precisely and efficiently bind deep into the ATP binding pocket of the kinase and potentially to circumvent the steric interference that results in resistance to bulkier kinase inhibitors, especially the solvent-front and gatekeeper mutations of ROS1, TRK, and ALK kinases.