Mefenamic acid inhibit transforming growth factor-beta type-1: Repurposing anti-inflammatory drugs in wound healing using in-silico approaches

Aspects of molecular medicine Pub Date : 2023-12-01 DOI:10.1016/j.amolm.2023.100031

Miah Roney , Abdul Rashid Issahaku , Normaiza Binti Zamri , Mohd Fadhlizil Fasihi Mohd Aluwi

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Abstract

Due to low cost and time-saving benefits, drug repurposing is a safe and successful method to discover drug. A druggable target for inflammation, transforming growth factor-beta type-1 (TGF-β 1) has been identified to be associated with wound healing. Finding the most effective TGF-β 1 inhibitor among FDA-approved anti-inflammatory medications was the goal of the current investigation. To find the best hits against TGF-β 1, we used structure-based virtual screening on medications that have received FDA approval. We discovered two FDA-approved medications with notable selectivity and affinity for the binding pocket of TGF-β 1. Mefenamic acid, one of these found hits, interacts with key TGF-β 1 residues and favourably attaches to the binding pocket, requiring further study. The kinetics of the binding between mefenamic acid and TGF-β 1 were revealed by all-atom precise molecular dynamics (MD) simulations. Mefenamic acid, which may also be used as a possible lead chemical against TGF-β 1, may be a promising TGF-β 1 inhibitor.

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甲非那明酸抑制转化生长因子-1型:用芯片方法在伤口愈合中重新利用消炎药

药物再利用具有成本低、节省时间的优点，是一种安全、成功的药物发现方法。转化生长因子-β -1 (TGF-β 1)是炎症的可药物靶点，已被确定与伤口愈合有关。在fda批准的抗炎药物中寻找最有效的TGF-β 1抑制剂是当前研究的目标。为了找到对抗TGF-β 1的最佳药物，我们对已获得FDA批准的药物进行了基于结构的虚拟筛选。我们发现了两种fda批准的药物，它们对TGF-β 1的结合袋具有显著的选择性和亲和力。甲氨酰胺酸是这些发现的靶点之一，它与关键的TGF-β 1残基相互作用，并有利地附着在结合袋上，这需要进一步的研究。通过全原子精确分子动力学(MD)模拟揭示了甲氨酰胺酸与TGF-β 1结合的动力学过程。甲氧胺酸可能是一种很有前途的TGF-β 1抑制剂，也可能作为抗TGF-β 1的先导化合物。

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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Aspects of molecular medicine Molecular Biology, Molecular Medicine

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38 days