國家衛生研究院 NHRI:Item 3990099045/7573

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Title:	Development drug candidate targeting EGFR kinase: DBPR112
Authors:	Sun, HY;Hsu, JTA;Chen, CT;Yeh, TK;Pan, SL;Chao, YS;Hsieh, HP
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	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 EGFR Wild-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.
Date:	2013-04-07
Relation:	Abstracts of Papers - American Chemical Society. 2013 Apr 7;245:Article number 299-MEDI.
Link to:	http://abstracts.acs.org/chem/245nm/program/view.php?pub_num=299&par=MEDI
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000324303602318
Appears in Collections:	[Hsing-Pang Hsieh] Conference Papers/Meeting Abstract [Yu-Sheng Chao(2002-2013)] Conference Papers/Meeting Abstract [Teng-Kuang Yeh] Conference Papers/Meeting Abstract [Shiow-Lin Pan(2009-2013)] Conference Papers/Meeting Abstract [John Tsu-An Hsu] Conference Papers/Meeting Abstract [Chiung-Tong Chen] Conference Papers/Meeting Abstract

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