PIM kinase inhibitors: Structural and pharmacological perspectives

被引:69
作者
Asati, Vivek [1 ]
Mahapatra, Debarshi Kar [2 ]
Bharti, Sanjay Kumar [3 ]
机构
[1] NRI Inst Pharm, Dept Pharmaceut Chem, Bhopal 462023, Madhya Pradesh, India
[2] Dadasaheb Balpande Coll Pharm, Dept Pharmaceut Chem, Nagpur 440037, Maharashtra, India
[3] Guru Ghasidas Vishwavidyalaya, Inst Pharmaceut Sci, Bilaspur 495009, Chhattisgarh, India
关键词
PIM kinase; Proliferation; Structure-activity relationship; Inhibitors; Mutation; Cancer; VITRO ANTIPROLIFERATIVE ACTIVITIES; SELECTIVE INHIBITORS; C-MYC; SERINE/THREONINE KINASES; BIOLOGICAL EVALUATION; POTENT; DISCOVERY; DESIGN; DERIVATIVES; ANTICANCER;
D O I
10.1016/j.ejmech.2019.03.050
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The PIM kinase, also known as serine/threonine kinase plays an important role in cancer biology and is found in three different isoforms namely PIM-1, PIM-2, and PIM-3. They are extensively distributed and are implicated in a variety of biological processes, including cell proliferation, cell differentiation, and apoptosis. They act as weak oncogene and whenever expressed in exacerbating forms are responsible for different types of human cancer. Recently, different isoforms of PIM kinase have been identified as a clinical biomarker and potential therapeutic target for personalized treatment of advanced cancer. The inhibition of PIM kinase has become a scientific interest and some inhibitors have been developed and/or are under different phases of clinical trials. Several medicinally privileged heterocyclic ring scaffolds such as pyrrole, pyrimidine, thiazolidine, benzofuran, indole, triazole, oxadiazole, and quinoline derivatives have been synthesized and evaluated for their PIM inhibitory activity. This review comprehensively focuses on pharmacological implications of PIM kinases in oncogenesis, structural insights of PIM inhibitors and their structure-activity relationships (SARs). (C) 2019 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:95 / 108
页数:14
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