Bioinformatics Institute (BII), Agency for Science, Technology and Research (A⁎STAR), 30 Biopolis Street, #07-01, Matrix, 138671, Singapore.
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A⁎STAR), 30 Biopolis Street, #07-01, Matrix, 138671, Singapore; Department of Biological Sciences (DBS), National University of Singapore (NUS), 8 Medical Drive, 117579, Singapore.
Curr Opin Struct Biol. 2020 Jun;62:149-157. doi: 10.1016/j.sbi.2020.01.010. Epub 2020 Feb 12.
Allosteric drugs have become an indispensable toolbox of rapidly developing precision medicine, having already established reputation of advantages over traditional medicines. Allosteric mechanisms are also widely involved in the action of SNPs and latent cancer drivers, and can be used in fine and specific tuning of biologics, providing a great potential in diagnostics and therapy. We discuss here major targets for prospected allosteric medicines, currently available allosteric compounds, and drug-candidates at different stages of research and (pre)clinical trials. We describe our computational model of the comprehensive allosteric control of protein activity, outlining the ways of implementing it in pharmacological applications. Finally, we formulate outstanding questions and discuss feasible directions in the work on allosteric drugs and mutations.
变构药物已成为快速发展的精准医学不可或缺的工具，其优势已经超越传统药物。变构机制也广泛涉及 SNP 和潜在癌症驱动因素的作用，可以用于精细和特异性地调节生物制剂，在诊断和治疗方面具有巨大潜力。在这里，我们讨论了预期变构药物的主要靶点、目前可用的变构化合物以及不同研究和（临床前）试验阶段的候选药物。我们描述了我们的蛋白质活性综合变构控制的计算模型，概述了在药理学应用中实现它的方法。最后，我们提出了在变构药物和突变研究方面的悬而未决的问题，并讨论了可行的方向。
