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设计小分子药物以通过稳定所需构象来解决蛋白质-蛋白质相互作用 (PPIs) 时的刚性重要性。

Importance of Rigidity in Designing Small Molecule Drugs To Tackle Protein-Protein Interactions (PPIs) through Stabilization of Desired Conformers.

机构信息

UCB , 216 Bath Road , Slough SL1 3WE , United Kingdom.

Bohicket Pharma Consulting LLC , 2556 Seabrook Island Road , Seabrook Island , South Carolina 29455 , United States.

出版信息

J Med Chem. 2018 May 24;61(10):4283-4289. doi: 10.1021/acs.jmedchem.7b01120. Epub 2017 Nov 28.

Abstract

Tackling PPIs, particularly by stabilizing clinically favored conformations of target proteins, with orally available, bona fide small molecules remains a significant but immensely worthwhile challenge for the pharmaceutical industry. Success may be more likely through the application of nature's learnings to build intrinsic rigidity into the design of clinical candidates.

摘要

解决质子泵抑制剂(PPIs)问题,特别是通过稳定临床青睐的靶蛋白构象,使用口服、真正的小分子药物仍然是制药行业面临的一个重大但非常有价值的挑战。通过应用自然的知识来构建临床候选药物的内在刚性,成功的可能性可能更大。

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