Recent Advances in the Development of Multi-Kinase Inhibitors

被引:87
作者
Krug, Martin [1 ]
Hilgeroth, Andreas [1 ]
机构
[1] Univ Halle Wittenberg, Inst Pharm, D-06120 Halle, Saale, Germany
关键词
Multiple targeted; kinase inhibitor; development;
D O I
10.2174/138955708786369591
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
During the last two decades, protein kinases have emerged as a major target for cancer therapy and a large number of selective kinase inhibitors have been developed as potential anticancer drugs. To avoid unpredictable toxic effects, researchers usually aim at designing highly selective inhibitors. But since the formation and progression of a tumor has to be considered as a multifactorial process, which is dependent on different signalling pathways, it seems reasonable to establish anticancer therapies that target several kinases associated with tumor growth. In general, this can be achieved by two different strategies, either by concomitantly using a combination of a set of selective kinase inhibitors or by administering a single agent, which simultaneously inhibits several kinases, a so called multi-kinase inhibitor. In this review, benefits and obstacles of both strategies are discussed. An overview over recently approved and newly upcoming multi-kinase inhibitors is given.
引用
收藏
页码:1312 / 1327
页数:16
相关论文
共 125 条
[21]   Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial [J].
Demetri, George D. ;
van Oosterom, Allan T. ;
Garrett, Christopher R. ;
Blackstein, Martin E. ;
Shah, Manisha H. ;
Verweij, Jaap ;
McArthur, Grant ;
Judson, Ian R. ;
Heinrich, Michael C. ;
Morgan, Jeffrey A. ;
Desai, Jayesh ;
D Fletcher, Christopher ;
George, Suzanne ;
Bello, Carlo L. ;
Huang, Xin ;
Baum, Charles M. ;
Casali, Paolo G. .
LANCET, 2006, 368 (9544) :1329-1338
[22]   Case Report 2. Severe erythema multiforme induced by two consecutive anti-angiogenic drugs [J].
Dilhuydy, Marie-Sarah ;
Jouary, Thomas ;
Gomez, Aurelie ;
Wallerand, Herve ;
Pasticier, Gilles ;
Rauaud, Alain .
EJC SUPPLEMENTS, 2007, 5 (07) :30-31
[23]   1,4-Dihydroindeno[1,2-c]pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel [J].
Dinges, Jurgen ;
Albert, Daniel H. ;
Arnold, Lee D. ;
Ashworth, Kimba L. ;
Akritopoulou-Zanze, Irini ;
Bousquet, Peter F. ;
Bouska, Jennifer J. ;
Cunha, George A. ;
Davidsen, Steven K. ;
Diaz, Gilbert J. ;
Djuric, Stevan W. ;
Gasiecki, Alan F. ;
Gintant, Gary A. ;
Gracias, Vijaya J. ;
Harris, Christopher M. ;
Houseman, Kathryn A. ;
Hutchins, Charles W. ;
Johnson, Eric F. ;
Li, Hu ;
Marcotte, Patrick A. ;
Martin, Ruth L. ;
Michaelides, Michael R. ;
Nyein, Michelle ;
Sowin, Thomas J. ;
Su, Zhi ;
Tapang, Paul H. ;
Xia, Zhiren ;
Zhang, Henry Q. .
JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (09) :2011-2029
[24]   Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors [J].
Dinges, Jurgen ;
Akritopoulou-Zanze, Irini ;
Arnold, Lee D. ;
Barlozzari, Teresa ;
Bousquet, Peter F. ;
Cunha, George A. ;
Ericsson, Anna M. ;
Iwasaki, Nobuhiko ;
Michaelides, Michael R. ;
Ogawa, Nobuo ;
Phelan, Kathleen M. ;
Rafferty, Paul ;
Sowin, Thomas J. ;
Stewart, Kent D. ;
Tokuyama, Ryukou ;
Xia, Zhiren ;
Zhang, Henry Q. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (16) :4371-4375
[25]   1,4-Dihydroindeno[1,2-c]pyrazoles as novel multitargeted receptor tyrosine kinase inhibitors [J].
Dinges, Jurgen ;
Ashworth, Kimba L. ;
Akritopolou-Zanze, Irini ;
Arnold, Lee D. ;
Baumeister, Steven A. ;
Bousquet, Peter F. ;
Cunha, George A. ;
Davidsen, Steven K. ;
Djuric, Stevan W. ;
Gracias, Vijaya J. ;
Michaelides, Michael R. ;
Rafferty, Paul ;
Sowin, Thomas J. ;
Stewart, Kent D. ;
Xia, Zhiren ;
Zhang, Henry Q. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (16) :4266-4271
[26]  
Erlichman C, 2001, CANCER RES, V61, P739
[27]   Sorafenib in advanced clear-cell renal-cell carcinoma [J].
Escudier, Bernard ;
Eisen, Tim ;
Stadler, Walter M. ;
Szczylik, Cezary ;
Oudard, Stephane ;
Siebels, Michael ;
Negrier, Sylvie ;
Chevreau, Christine ;
Solska, Ewa ;
Desai, Apurva A. ;
Rolland, Frederic ;
Demkow, Tomasz ;
Hutson, Thomas E. ;
Gore, Martin ;
Freeman, Scott ;
Schwartz, Brian ;
Shan, Minghua ;
Simantov, Ronit ;
Bukowski, Ronald M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :125-134
[28]   New dual inhibitors of EGFR and HER2 protein tyrosine kinases [J].
Fink, BE ;
Vite, GD ;
Mastalerz, H ;
Kadow, JF ;
Kim, SH ;
Leavitt, KJ ;
Du, K ;
Crews, D ;
Wong, TW ;
Hunt, JT ;
Vyas, DM ;
Tokarski, JS .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (21) :4774-4779
[29]   Playing dirty [J].
Frantz, S .
NATURE, 2005, 437 (7061) :942-943
[30]   A phase I clinical and pharmacokinetic study of oral CI-1033 in combination with docetaxel in patients with advanced solid tumors [J].
Garland, Linda L. ;
Hidalgo, Manuel ;
Mendelson, David S. ;
Ryan, David P. ;
Arun, Banu K. ;
Lovalvo, Jennifer L. ;
Eiseman, Irene A. ;
Olson, Stephen C. ;
Lenehan, Peter F. ;
Eder, Joseph P. .
CLINICAL CANCER RESEARCH, 2006, 12 (14) :4274-4282