molecules of the month

The Turning Point Therapeutics oral, brain-penetrant ALK/ROS1/TRK kinase inhibitor, repotrectinib (TPX-0005), is a macrocyclic molecule with a small size intended to limit adverse interactions with resistance mutation hotspots near kinase active sites. TRK fusion proteins are driver mutations in certain cancers (which respond well to larotrectinib and entrectinib) but resistance is anticipated to be a problem. This molecule inhibits TRKA, TRKB, TRC, ROS1, and various forms of ALK, and durable responses were observed in both TKI-naïve and pretreated patients with NTRK+ cancers (NCT03093116).