TMPK inhibitors(Ghent University)(TMPK inhibitors(Ghent University)) - 药物靶点：DTYMK_在研适应症：易感染结核分枝杆菌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

alpha-Thymidine derivative 15(Ghent University)

靶点

DTYMK

作用机制

DTYMK inhibitors(deoxythymidylate kinase inhibitors)

治疗领域

感染其他疾病

在研适应症

易感染结核分枝杆菌

非在研适应症-

原研机构

Ghent University

在研机构

Ghent University

非在研机构-

最高研发阶段药物发现

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C18H18ClF3N4O4S

InChIKeyIJDGQXGQAWBJEG-MJBXVCDLSA-N

CAS号954117-16-9

关联

100 项与 TMPK inhibitors(Ghent University) 相关的临床结果

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100 项与 TMPK inhibitors(Ghent University) 相关的转化医学

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100 项与 TMPK inhibitors(Ghent University) 相关的专利（医药）

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1

项与 TMPK inhibitors(Ghent University) 相关的文献（医药）

2024-12-31·Journal of Enzyme Inhibition and Medicinal Chemistry

Challenging the Biginelli scaffold to surpass the first line antitubercular drugs: Mycobacterium tuberculosis thymidine monophosphate kinase (TMPK mt ) inhibition activity and molecular modelling studies

Article

作者: Mahran, Mona A. ; Shehat, Michael G. ; Atta, Amal ; Fahmy, Salwa ; Sriram, Dharmarajan ; Labouta, Ibrahim M. ; El-Shoukrofy, Mai S.

New Biginelli adducts were rationalised, via the introduction of selected anti-tubercular (TB) pharmacophores into the dihydropyrimidine (DHPM) ring of deoxythymidine monophosphate (dTMP), the natural substrate of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt). Repurposing was one of the design rationale strategies for some selected mimics of the designed compounds. The anti-TB activity was screened against the Mtb H₃₇Rv strain where 11a was superior to ethambutol (EMB), and was 9-fold more potent than pyrazinamide (PZA). Additionally, compounds 11b, 4a, 4b, 13a, 13b and 14a elicited higher anti-TB activity than PZA, showing better safety profiles than EMB against RAW 264.7 cells' growth. The in vitro TMPKmt inhibition assay released compounds 11a, 11b and 13b as the most potent inhibitors. Docking studies presumed the binding modes and molecular dynamics (MD) simulation revealed the dynamic stability of 11a-TMPKmt complex over 100 ns. In silico prediction of the chemo-informatics properties of the most active compounds was conducted.

100 项与 TMPK inhibitors(Ghent University) 相关的药物交易

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