Lung cancer is one of the chief causes of cancer death in the world; in addition, non-small cell lung cancer (NSCLC) accounts for 85% of the lung cancer deaths. The development of tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have shown remarkable effects in patients but some acquired resistance after treatment. Therefore, the discovery of efficacious EGFR-TKIs poses an utmost priority. Our team at IBPR has designed and synthesized a series of compounds by high throughput parallel synthesis platform and then identified DBPR112 as a potent EGFR-TKI clinical candidate, showing IC50 of 2 nM in HCC827 cells, and excellent inhibitory ability on EGFRWT and EGFRDM. DBPR112 was orally effective against the growth of human lung HCC827 tumors subcutaneously xenografted in nude mice. A dramatic reduction in tumor size was noted with DBPR112 treatment, while displaying negligible body weight loss in all dosing groups. Futhermore, DBPR112 was more tolerable than afatinib in mice. To date, all pre-clinical studies were completed, the IND application of DBPR112 was approved by US FDA and the Phase I clinical trial protocol was also approved by Taiwan FDA.
