TGRX-678

TGRX-678 is a novel, orally bioavailable small molecule allosteric inhibitor of the BCR-ABL1 tyrosine kinase, specifically designed to target the myristoyl pocket (STAMP) of ABL1. It is being developed for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph-CML), including patients with resistance mutations such as T315I and those who have failed prior tyrosine kinase inhibitors (TKIs), including third-generation TKIs and STAMP inhibitors. Preclinical studies demonstrate potent anti-leukemia activity against native BCR-ABL1 and clinically relevant ATP-site mutants with minimal off-target cytotoxicity. Clinical trials show promising efficacy in both chronic phase (CP) and accelerated phase (AP) CML patients, including those with T315I mutation or prior 3G-TKI/STAMP inhibitor failure. The drug exhibits favorable pharmacokinetics with a long half-life (>100 hours). TGRX-678 is currently in Phase 1 clinical trials in the US and China, as well as ongoing Phase 2 trials in China[1][2][4][5][6][8].