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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(04): e207-e222
DOI: 10.1055/s-0042-1758692
Review Article

Recent Research Advances in Small-Molecule Pan-PIM Inhibitors

Lei Xu
1   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Yu-Cheng Meng
1   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Peng Guo
1   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Ming Li
1   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Lei Shao
2   Microbial Pharmacology Laboratory, Shanghai University of Medicine and Health Sciences, Shanghai, People's Republic of China
,
Jun-Hai Huang
1   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
› Author Affiliations Funding The work was approved by the Natural Science Foundation of Shanghai with Grant No. 19ZR1437900.
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Abstract

PIM kinase is consequently emerging as a promising target for cancer therapeutics and immunomodulation. PIM kinases are overexpressed in a variety of hematological malignancies and solid tumors, and their inhibition has become a strong therapeutic interest. Currently, some pan-PIM kinase inhibitors are being developed under different phases of clinical trials. Based on the different scaffold structures, they can be classified into various subclasses. The X-ray structure of the kinase complex outlines the rationale of hit compound confirmation in the early stage. Structure–activity relationships allow us to rationally explore chemical space and further optimize multiple physicochemical and biological properties. This review focuses on the discovery and development of small-molecule pan-PIM kinase inhibitors in the current research, and hopes to provide guidance for future exploration of the inhibitors.

Keywords

pan-PIM inhibitors - structure classification - lead optimization - structure–activity relationship


Publication History

Received: 23 May 2022

Accepted: 14 October 2022

Article published online:
27 December 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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