JAK3 inhibitor VI

JAK3 inhibitor VI is a small molecule tyrosine kinase inhibitor originally designed to inhibit **Janus kinase 3 (JAK3)**, but found to selectively inhibit the mutant form of the **epidermal growth factor receptor (EGFR)** with gatekeeper mutation **T790M/L858R**, which is associated with resistance to EGFR inhibitors in non-small cell lung cancer (NSCLC). It shows stronger activity against EGFR T790M/L858R than against wild-type EGFR, and also suppresses proliferation of EGFR T790M/L858R-positive cells. Structurally, it is an indol-based compound modeled to interact via hydrogen bonds within the ATP-binding pocket of mutant EGFR. Its original mechanism involves inhibition of JAK3, but its activity against mutant EGFR is not due to JAK3 inhibition. Development is primarily reported in preclinical research as a tool compound for EGFR T790M mutation[1].