Repotrectinib

Resistance mutations that blunt first-generation inhibitors were the design target for repotrectinib, a next-generation inhibitor of ROS1 and the tropomyosin receptor kinases. Non-small cell lung cancer driven by ROS1 gene fusions is its principal application, including disease that has already progressed on earlier targeted agents. By retaining affinity for the altered kinase domains that confer resistance, the compound addresses the sequence of escape mutations that typically limits the duration of benefit from the first inhibitor in a fusion-positive tumour. The molecule is a small molecule with the formula C18H18FN5O2 and a molecular weight of approximately 355.4 g/mol. It is an approved agent that has reached the final phase of clinical development.

SMILES

C[C@H]1CNC(=O)c2cnn3ccc(nc23)N[C@H](C)c2cc(F)ccc2O1

InChI

InChI=1S/C18H18FN5O2/c1-10-8-20-18(25)14-9-21-24-6-5-16(23-17(14)24)22-11(2)13-7-12(19)3-4-15(13)26-10/h3-7,9-11H,8H2,1-2H3,(H,20,25)(H,22,23)/t10-,11+/m0/s1