α-杂芳基硫甲基酮：3CLpro的小分子抑制剂。

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI:10.2478/acph-2025-0023

Damijan Knez, Matic Proj, Krištof Bozovičar, Stanislav Gobec

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引用次数: 0

摘要

SARS-CoV-2病毒的主要蛋白酶3CLpro是治疗COVID-19的既定治疗靶点。在本研究中，我们筛选了一个内部化合物文库，鉴定出一系列α-杂芳基硫甲基酮作为3CLpro的抑制剂。其中，类似物31和33的IC 50值分别为95.4±3.1和95.0±6.9µmol L- 1，是最有兴趣的候选物。初步的体外研究表明一种潜在的共价抑制模式，尽管需要进一步的研究来证实这一机制。这些发现为3clpro靶向抑制剂的开发提供了新的化学支架。

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α-Heteroarylthiomethyl ketones: Small molecule inhibitors of 3CL^pro.

The main protease 3CL^pro of the SARS-CoV-2 virus is a well--established therapeutic target for the treatment of COVID-19. In this study, we screened an in-house compound library and identified a series of α-heteroarylthiomethyl ketones as inhibitors of 3CL^pro. Among these, analogues 31 and 33 emerged as the most interesting candidates with IC ₅₀ values of 95.4 ± 3.1 and 95.0 ± 6.9 µmol L^- ¹, respectively. Preliminary in vitro studies suggest a potential covalent mode of inhibition, although further studies are required to confirm this mechanism. These findings provide a new chemical scaffold for the development of 3CL^pro-targeting inhibitors.

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来源期刊

Acta Pharmaceutica PHARMACOLOGY & PHARMACY-

CiteScore

5.20

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： AP is an international, multidisciplinary journal devoted to pharmaceutical and allied sciences and contains articles predominantly on core biomedical and health subjects. The aim of AP is to increase the impact of pharmaceutical research in academia, industry and laboratories. With strong emphasis on quality and originality, AP publishes reports from the discovery of a drug up to clinical practice. Topics covered are: analytics, biochemistry, biopharmaceutics, biotechnology, cell biology, cell cultures, clinical pharmacy, drug design, drug delivery, drug disposition, drug stability, gene technology, medicine (including diagnostics and therapy), medicinal chemistry, metabolism, molecular modeling, pharmacology (clinical and animal), peptide and protein chemistry, pharmacognosy, pharmacoepidemiology, pharmacoeconomics, pharmacodynamics and pharmacokinetics, protein design, radiopharmaceuticals, and toxicology.