WZ4002 is an irreversiblely inhibitor against EGFR T790M (mutation of the gatekeeper T790 residue) which is detected in 50% of clinically resistant patients to gefitinib or erlotinib. WZ4002 has a basic chemical framework (covalent pyrimidine) which is different from that of other EGFR inhibitors. [1]
This agent is 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wildtype EGFR, than quinazoline-based EGFR inhibitors (HKI-272 and CL-387,785) in vitro. [1]
This agent has a 300-fold lower half-maximum inhibitory concentration (IC50<20nM) against the PC9GR(delE746_A750/T790M, gefitinib-resistant) cells compared with clinical-stage inhibitors such as HKI-272. [1]
In a 2-week efficacy study, WZ4002 treatment resulted in significant tumour regressions compared with vehicle alone in both T790M-containing murine models. |
