|
Type |
Poster Presentation |
Area |
Medicinal Chemistry |
Room No. |
Event Hall |
Time |
4월 19일 (목요일) 11:00~12:30 |
Code |
MEDI.P-642 |
Subject |
Discovery of Mutant-Selective BCR/ABL-T315I Inhibitors with Reduced Adverse Effects |
Authors |
Yunju Nam, Taebo Sim1,* KU-KIST, Korea University, Korea 1Chemical Kinomics Research Center, Korea Institute of Science and Technology, Korea |
Abstract |
Chronic myeloid leukemia (CML) has been overcome by the development of imatinib, the small-molecule inhibitor of BCR/ABL kinase. However, resistance to imatinib mainly derived from point mutation in gatekeeper region (T315I) has motivated the development of next generation BCR/ABL inhibitors. Ponatinib is the only clinically approved tyrosine kinase inhibitor that overcomes BCR/ABL-T315I mutant, however it shows cardiotoxic adverse effects such as vascular occlusive events derived from its significant VEGFR2 inhibitory activity. Herein, we report novel 1,6-disubstituted-1H-indole derivatives as highly potent on BCR/ABL-T315I with marginal VEGFR2 inhibition. Among them, pharmacologically optimized compound 6d displayed significant in vivo efficacy in bioluminescent xenograft models using BCR/ABL-T315I Ba/F3 cell lines without notable adverse effects. |
E-mail |
yunjunam33@gmail.com |
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