A selective “Pan-TRK” Inhibitor

The neurotrophin tyrosine receptor kinase (NTRK) family composed of three members, TRKA, TRKB, and TRKC. These Tropomyosin receptor kinase (TRK) proteins are single-pass transmembrane proteins, expressed in the nervous system and in many non-neuronal tissue types. It has been observed that the occurrence of NTRK gene fusion between NTRK1, 2, or 3 and various unrelated gene partners, represents the genomic alteration with oncogenic potential, which has been observed in a wide range of human tumor types in comparison to oncogenic mechanisms.

1st generation TRK inhibitors including larotrectinib and entrectinib have demonstrated clinical benefit in patients with solid malignancies harboring oncogenic NTRK fusions. Solvent front mutation, gatekeeper mutation, and glycine mutation of DFG at the beginning of the A-loop have been reported in clinical trials from larotrectinib- and entrectinib-refractory patients.

AUM601 is a highly selective, orally administered, which inhibits not only pan-TRK(TRKA, TRKB, and TRKC), but also resistance mutations of TRKs, by blocking the activity of tyrosine kinases.