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Park, Cheol-Min
Synthetic & Medicinal Chemistry Lab
Research Interests
  • Organic synthesis, medicinal chemistry, chemical biology


ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

DC Field Value Language Souers, Andrew J. ko Leverson, Joel D. ko Boghaert, Erwin R. ko Ackler, Scott L. ko Catron, Nathaniel D. ko Chen, Jun ko Dayton, Brian D. ko Ding, Hong ko Enschede, Sari H. ko Fairbrother, Wayne J. ko Huang, David C. S. ko Hymowitz, Sarah G. ko Jin, Sha ko Khaw, Seong Lin ko Kovar, Peter J. ko Lam, Lloyd T. ko Lee, Jackie ko Maecker, Heather L. ko Marsh, Kennan C. ko Mason, Kylie D. ko Mitten, Michael J. ko Nimmer, Paul M. ko Oleksijew, Anatol ko Park, Chang H. ko Park, Cheol-Min ko Phillips, Darren C. ko Roberts, Andrew W. ko Sampath, Deepak ko Seymour, John F. ko Smith, Morey L. ko Sullivan, Gerard M. ko Tahir, Stephen K. ko Tse, Chris ko Wendt, Michael D. ko Xiao, Yu ko Xue, John C. ko Zhang, Haichao ko Humerickhouse, Rod A. ko Rosenberg, Saul H. ko Elmore, Steven W. ko 2014-11-11T00:15:47Z - 2014-11-10 ko 2013-02 -
dc.identifier.citation NATURE MEDICINE, v.19, no.2, pp.202 - 208 ko
dc.identifier.issn 1078-8956 ko
dc.identifier.uri -
dc.identifier.uri ko
dc.description.abstract Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X L), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-X L inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers. ko
dc.description.statementofresponsibility close -
dc.language ENG ko
dc.subject B-CELL LYMPHOMA ko
dc.subject FAMILY INHIBITOR ko
dc.subject INDUCE APOPTOSIS ko
dc.subject HIGH-AFFINITY ko
dc.subject IN-VIVO ko
dc.subject EXPRESSION ko
dc.subject CANCER ko
dc.title ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets ko
dc.type ARTICLE ko
dc.identifier.scopusid 2-s2.0-84873540049 ko
dc.identifier.wosid 000314675900028 ko
dc.type.rims ART ko
dc.description.wostc 201 *
dc.description.scopustc 136 * 2015-05-06 * 2014-11-10 *
dc.identifier.doi 10.1038/nm.3048 ko
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