VX-680/MK-0457 - Aurora kinase inhibitor oncolytic

被引：8

作者：

Wang, Y. ^{[1
]}

Serradell, N. ^{[1
]}

机构：

[1] Prous Sci, E-08080 Barcelona, Spain

来源：

DRUGS OF THE FUTURE | 2007年 / 32卷 / 02期

关键词：

D O I：

10.1358/dof.2007.032.02.1076496

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

VX-680/MK-0457 is a small-molecule Aurora kinase inhibitor with inhibition constants (K(i)) of 0.6, 18 and 4.6 nM for Aurora kinase A, B and C, respectively; it also inhibits Flt-3 and AN kinases, particularly mutant forms. The compound displays potent antitumor activity in a broad range of cancer cell lines and is well tolerated in preclinical studies. A phase I clinical trial of VX-680/MK-0457 was carried out in patients with chronic myeloid leukemia (CML) or acute lymphocytic leukemia (ALL) with the T315l Bcr-Abl resistance mutation and patients with refractory JAK2-positive myeloproliferative disease. VX-680/MK-0457 demonstrated encouraging antitumor activity and a good overall safety profile.

引用

页码：144 / 147

页数：4

共 50 条

[31] MK-0457, an Aurora kinase and BCR–ABL inhibitor, is active in patients with BCR–ABL T315I leukemia
F J Giles
R T Swords
A Nagler
A Hochhaus
O G Ottmann
D A Rizzieri
M Talpaz
J Clark
P Watson
A Xiao
B Zhao
D Bergstrom
P D Le Coutre
S J Freedman
J E Cortes
Leukemia, 2013, 27 : 113 - 117
[32] Crystal Structure of Human Aurora B in Complex with INCENP and VX-680
Elkins, Jonathan M.
Santaguida, Stefano
Musacchio, Andrea
Knapp, Stefan
JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (17) : 7841 - 7848
[33] Co-treatment with aurora kinase inhibitor MK-0457 and pan-histone deacetylase inhibitor vorinostat: A novel targeted treatment for AML and CML
Ustun, C.
Fiskus, W.
Wang, Y.
Rao, R.
Lee, P.
Kolhe, R.
Fernandez, P.
Jillella, A. P.
Buser, C.
Bhalla, K. N.
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (15)
[34] MK-0457 is a novel aurora kinaseand janus kinase 2 inhibitor with activity in transformed JAK2-positive myeloproliferative disease
Giles, J.
Bergstrom, V. D. A.
Garcia-Manero, G.
Kornblau, S.
Andreeff, M.
Jones, D.
Freedman, S. J.
Verstovsek, S.
Kantarjian, H.
Rizzieri, D.
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2007, 92 : 243 - 244
[35] VX-680, a novel small molecule inhibitor of the Aurora kinases, suppresses tumour growth in vivo.
Harrington, L
CLINICAL CANCER RESEARCH, 2003, 9 (16) : 6226S - 6226S
[36] Modulation of kinase-inhibitor interactions by auxiliary protein binding: Crystallography studies on Aurora A interactions with VX-680 and with TPX2
Zhao, Baoguang
Smallwood, Angela
Yang, Jingsong
Koretke, Kristin
Nurse, Kelvin
Calamari, Amy
Kirkpatrick, Robert B.
Lai, Zhihong
PROTEIN SCIENCE, 2008, 17 (10) : 1791 - 1797
[37] MK-0457 is a novel aurora kinase and janus kinase 2 (JAK2) inhibitor with activity in transformed JAK2-Positive myeloproliferative disease (MPD).
Giles, Francis
Bergstrom, Donald A.
Garcia-Manero, Guillermo
Kornblau, Steven
Andreeff, Michael
Kantarjan, Hagop
Jones, Dan
Freedman, Steven J.
Verstovsek, Srdan
BLOOD, 2006, 108 (11) : 309B - 310B
[38] MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia
Giles, F. J.
Swords, R. T.
Nagler, A.
Hochhaus, A.
Ottmann, O. G.
Rizzieri, D. A.
Talpaz, M.
Clark, J.
Watson, P.
Xiao, A.
Zhao, B.
Bergstrom, D.
Le Coutre, P. D.
Freedman, S. J.
Cortes, J. E.
LEUKEMIA, 2013, 27 (01) : 113 - 117
[39] SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers
Tagal, Vural
Wei, Shuguang
Zhang, Wei
Brekken, Rolf A.
Posner, Bruce A.
Peyton, Michael
Girard, Luc
Hwang, TaeHyun
Wheeler, David A.
Minna, John D.
White, Michael A.
Gazdar, Adi F.
Roth, Michael G.
NATURE COMMUNICATIONS, 2017, 8
[40] Metabolism of MK-0457, a potent aurora kinase inhibitor: Interspecies comparison and role of human cytochrome p450 and flavin-containing monooxygenase
Ballard, J. E.
Prueksaritanont, T.
Tang, C.
DRUG METABOLISM AND DISPOSITION, 2007, 35 (09) : 1447 - 1451

← 1 2 3 4 5 →