Lung cancer is the major cause of cancer death in the world while non small cell lung cancer (NSCLC) accounts approximately 85% of all lung cancer diagnosis. EGFR mutations, found in 10�30% of patients with NSCLC characterize a subpopulation with exquisite sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, the clinical benefits of first-generation TKIs (like gefitinib) can be further improved because of the development of drug-acquired resistance within 10�14 months in patients who initially respond to the treatment. Therefore, there is a need to discover next generation medicines as EGFR-TKIs for NSCLC patients. Currently, we had identified DBPR112 as a potent EGFR-TKI with oral in vivo activity in a mouse model for lung adenocarcinoma. DBPR112 showed IC50 of 2 nM in HCC827 cells and potent EGFRWild-Type (IC50: 10 nM) and EGFRL858R/T790M (IC50: 70 nM) kinase inhibition which are better than gefitinib and similar to that of BIBW2992 (afatinib, developed by Boehringer Ingelheim) that is currently under phase III clinical trial. DBPR112 was orally administered against the growth of human lung HCC827 tumors subcutaneously xenografted in nude mice. A dramatic reduction of the tumor size was noted in the tumors treated with DBPR112 without significant loss of body weights in the nude mice. In addition, the pharmacokinetics properties of DBPR112 are superior to those of BIBW2992. These results demonstrate the potential of DBPR112 as a therapeutic candidate for the treatment of lung adenocarcinoma with EGFR mutations.

Development drug candidate targeting EGFR kinase: DBPR112

245th National Meeting (2013)

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