Allosteric inhibitors for the treatment of cancers (2021-): A review from medicinal chemistry perspectives

IF 4 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-06-12 DOI:10.1016/j.molstruc.2025.142985

Fangli Ma , Yumei Chen , Yudie Ni , Huan He, Oulian Ji, Xizheng Quan, Baohui Qi

引用次数: 0

Abstract

Dysregulation of protein allostery is associated with a broad spectrum of human diseases. Generally, allosteric sites are structurally, conformationally and functionally different from the corresponding orthosteric pockets. In comparison to traditional medicines targeting orthosteric sites, allosteric drugs have already established reputation of advantages in improving selectivity profiles, reducing off-target effects, and overcoming acquired resistance, etc. Therefore, great efforts have been made in the development of effective allosteric modulators since the first allosteric drug was approved. This review summarizes recent advances of allosteric inhibitors for the treatment of cancers from a medicinal chemistry perspective. Furthermore, the current design and discovery strategies were also discussed in order to provide insight into the discovery of potential allosteric inhibitors for the treatment of cancers.

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变构抑制剂治疗癌症（2021-）：从药物化学的角度回顾

蛋白质变构失调与广泛的人类疾病有关。一般来说，变构位点在结构、构象和功能上都不同于相应的正构袋。与传统靶向正构位点的药物相比，变构药物在提高选择性、减少脱靶效应和克服获得性耐药等方面已经建立了良好的声誉。因此，自第一种抗变构药物被批准以来，人们在开发有效的抗变构调节剂方面做出了巨大的努力。本文从药物化学的角度综述了变构抑制剂治疗癌症的最新进展。此外，还讨论了当前的设计和发现策略，以便为发现治疗癌症的潜在变构抑制剂提供见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.