Type II Kinase Inhibitors: An Opportunity in Cancer for Rational Design

被引：80

作者：

Blanc, Javier ^{[1
]}

Geney, Raphael ^{[2
]}

Menet, Christel ^{[1
]}

机构：

[1] Galapagos NV, Dept Med Chem, B-2800 Mechelen, Belgium

[2] Galapagos SASU, Dept Computat & Struct Sci, Romainville, France

来源：

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY | 2013年 / 13卷 / 05期

关键词：

Allosteric inhibitors; cancer; covalent inhibitors; DFG-in; DFG-out; kinase inhibitors; Type I inhibitors; Type II inhibitors; Type III inhibitors; Type IV inhibitors; CHRONIC MYELOID-LEUKEMIA; RECEPTOR TYROSINE KINASES; ENDOTHELIAL GROWTH-FACTOR; SMALL-MOLECULE INHIBITORS; BCR-ABL INHIBITOR; P38 MAP KINASE; ALPHA-1-ACID GLYCOPROTEIN; MULTIKINASE INHIBITOR; STRUCTURAL MECHANISM; DASATINIB BMS-354825;

D O I：

10.2174/1871520611313050008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

With the advent of the Type II kinase inhibitor imatinib (Gleevec) for treatment against cancer, rational design of tailored molecules has brought a revolution in medicinal chemistry for treating tumours caused by kinase malfunctioning. Among different types of kinase inhibitors, the design of Type II inhibitors has been rationalized for maximizing the benefits and reducing drawbacks. Here we highlight the development made in Type II inhibitors, discussing the advantages and disadvantages of these types of molecules. Furthermore, we present the strategies for designing druggable molecules that either selectively inhibit target kinases or overcome drug resistance.

引用

页码：731 / 747

页数：17

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