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Volume 3, Issue 4 (Suppl)
Polym Sci
ISSN: 2471-9935 Polym Sci, an open access journal
October 12-13, 2017 Osaka, Japan
Annual Meeting on
Biopolymers and Drug Delivery Systems
Biopolymers Meeting 2017
October 12-13 2017
Page 44
Drug discovery of FLT-3/c-KIT inhibitors as anticancer drugs
Min-Hsien Wang, Chung-Yu Huang, Ching-Ping Chen, Ling-Hui Chou, Tsu Hsu, Chen-Tai Lu, Wen-Hsing Lin, Weir-Torn Jiaang, Teng-Kuang Yeh, Joe C Shih and
Chiung-Tong Chen
National Health Research Institutes, Taiwan
A
cute Myeloid Leukemia (AML) is an aggressive disease in which the rapid growth of abnormal leukemic cells in bone marrow
inhibits the production of normal blood cells. Genetic mutations, such as FLT3 and c-KIT, play their roles in the stepwise
leukemogenesis. The most frequent mutations among AML are FLT3 mutations. However, c-KIT mutations account for predicted
higher relapse rate and less overall survival. Because development of point mutations or gene amplification of target proteins results
in resistance of tyrosine kinase inhibitors, the use of a multi-targeted therapeutic approach is of potential clinical benefit. Several
multi-targeted tyrosine kinase inhibitors have been developed toward clinical uses for treating AML, pancreatic cancer, non-small cell
lung cancer, etc. They showed inhibitions of ABL, FLT3, c-KIT, RET, PDGFR, SRC and VEGFRs and an activity spectrum similar to
tyrosine kinases-targeted drugs on the market. In the present study, a novel small molecular multi-targeted tyrosine kinase inhibitor
DBPR487 was examined in
in vitro
kinase inhibition and cytotoxicity assays and evaluated for
in vivo
tumor growth inhibition
efficacies. Furthermore, the plasma samples collected from the rats orally administered with DBPR487 were measured to determine
the pharmacokinetic profile of DBPR487. Further preclinical toxicology and safety pharmacology studies are undergoing toward
clinical development.
Biography
Min-Hsien Wang is a Research Assistant in Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes (NHRI). Her research
interest is on drug discovery and development. Her work focuses on in vivo efficacy evaluation in rodents, establishment of disease animal models and toxicology
study in rats. She has experiences on animal handling, compounds dosing in different routes and blood collection in animals. She has discovered lead compounds
for a diabetes drug candidate (DBPR108) and anti-cancer drug candidates (DBPR112, DBPR114, DBPR115). She has publications in reputed journals which include
Bioorganic & Medicinal Chemistry Letters Journal, Journal of Medicinal Chemistry and European Journal of Medicinal Chemistry.
aruders@nhri.org.twMin-Hsien Wang et al., Polym Sci 2017, 3:4
DOI: 10.4172/2471-9935-C1-006