Protein targets of medicinally active molecules based on their original structures and molecular probes
10.16438/j.0513-4870.2019-1039
- VernacularTitle:基于分子原型和分子探针的药用活性分子蛋白作用靶标研究
- Author:
Wan-qi YANG
1
;
Chong-jing ZHANG
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
chemical proteomics;
activity-based protein profiling;
cellular thermal shift assay;
target identification;
rug development
- From:
Acta Pharmaceutica Sinica
2020;55(7):1439-1452
- CountryChina
- Language:Chinese
-
Abstract:
Medicinally active molecules are those that have pharmacological effects. Research on protein targets of these molecules not only clarifies their mechanism of action, but also deepens our understanding of biological systems. Here we review recent advances in protein targets of drugs used in clinical practice or in preclinical research. They have various functions including anti-inflammatory, anti-malarial, anti-tumor and other biological activities. Activity-based protein profiling (ABPP) and cellular thermal shift assay (CETSA) are two useful methods to identify the protein targets of small molecules. ABPP depends on a derivative active molecule probe to pull down the protein targets to reveal the interaction mechanisms between the active molecules and targets. Drug target engagement also can be assessed by means of CETSA based on ligand-induced changes in protein thermal stability. In the CETSA approach, the active molecules do not need to be chemically modified. Combining the CETSA method with quantitative mass spectrometry is an effective approach to study the effect of compounds on the thermal profile of a cellular proteome and identify the protein targets. ABPP and CETSA can be complementary and effectively clarify the protein targets. The study of protein targets will help reveal the mechanism of action of medicinal molecules, reveal toxic mechanisms and aid in the discovery of new medicinal targets to promote the process of drug development.
