Recent Advances in the Development of Multi-Kinase Inhibitors

被引:86
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
[1]   Phase II study of sorafenib in patients with advanced hepatocellular carcinoma [J].
Abou-Alfa, Ghassan K. ;
Schwartz, Lawrence ;
Ricci, Sergio ;
Amadori, Dino ;
Santoro, Armando ;
Figer, Arie ;
De Greve, Jacques ;
Douillard, Jean-Yves ;
Lathia, Chetan ;
Schwartz, Brian ;
Taylor, Ian ;
Moscovici, Marius ;
Saltz, Leonard B. .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (26) :4293-4300
[2]  
Ako E, 2007, ONCOL REP, V17, P887
[3]   Synthesis and biological evaluation of 5-substituted 1,4-dihydroindeno[1,2-c]pyrazoles as multitargeted receptor tyrosine kinase inhibitors [J].
Akritopoulou-Zanze, Irim ;
Albert, Daniel H. ;
Bousquet, Peter F. ;
Cunha, George A. ;
Harris, Christopher M. ;
Moskey, Maria ;
Dinges, Jurgen ;
Stewart, Kent D. ;
Sowin, Thomas J. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (11) :3136-3140
[4]  
[Anonymous], J CLIN ONCOL
[5]   New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis [J].
Bold, G ;
Altmann, KH ;
Frei, J ;
Lang, M ;
Manley, PW ;
Traxler, P ;
Wietfeld, B ;
Brüggen, J ;
Buchdunger, E ;
Cozens, R ;
Ferrari, S ;
Furet, P ;
Hofmann, F ;
Martiny-Baron, G ;
Mestan, J ;
Rösel, J ;
Sills, M ;
Stover, D ;
Acemoglu, F ;
Boss, E ;
Emmenegger, R ;
Lässer, L ;
Masso, E ;
Roth, R ;
Schlachter, C ;
Vetterli, W ;
Wyss, D ;
Wood, JM .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (12) :2310-2323
[6]  
Boschelli Diane H., 2002, Current Topics in Medicinal Chemistry, V2, P1051, DOI 10.2174/1568026023393354
[7]  
Bruns Christiane J., 2003, Proceedings of the American Association for Cancer Research Annual Meeting, V44, P604
[8]  
Bruns CJ, 2000, CANCER RES, V60, P2926
[9]  
Buchdunger E, 2000, J PHARMACOL EXP THER, V295, P139
[10]   Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas [J].
Burris, HA ;
Hurwitz, HI ;
Dees, EC ;
Dowlati, A ;
Blackwell, KL ;
O'Neil, B ;
Marcom, PK ;
Ellis, MJ ;
Overmoyer, B ;
Jones, SF ;
Harris, JL ;
Smith, DA ;
Koch, KM ;
Stead, A ;
Mangum, S ;
Spector, NL .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (23) :5305-5313