Research progress on irreversible tyrosine kinase inhibitors
10.3969/j.issn.1001-1978.2015.06.003
- VernacularTitle:不可逆性酪氨酸激酶抑制剂的研究进展
- Author:
Jianjun GUO
;
Jing ZHU
;
Yongyue ZHAO
;
Tengfei QUAN
;
Zhenyu MIAO
;
Haizhi BU
- Publication Type:Journal Article
- Keywords:
tyrosine kinase;
inhibitor;
anti-tumor drug;
irre-versible;
covalent binding;
ErbB;
BTK
- From:
Chinese Pharmacological Bulletin
2015;(6):749-754
- CountryChina
- Language:Chinese
-
Abstract:
Dysfunction in tyrosine kinase activity disrupts the nor-mal control of cellular phosphorylation signaling pathways,which plays a vital role in genesis and development of various tumors, and makes tyrosine kinases a class of targets of many anti-tumor drugs. Currently most approved tyrosine kinase inhibitors ( TKIs) are based on irreversible binding mechanisms, making them poorly selective, not potent or sustained enough regarding pharmacological effects and prone to triggering resistance. In the past decade, much progress has been made in the development of
a new class of TKIs which irreversibly inhibit their target proteins via the formation of covalent bonds, overcoming the drawbacks of irreversible TKIs. Several irreversible TKIs have entered markets or clinical research phases. This review is to summarize the structural, pharmacological and medicinal chemical properties of investigational and marketed irreversible TKIs as well as their re-cent developments.
