组蛋白脱乙酰酶 3 (HDAC3) 是组蛋白脱乙酰酶家族的一员，它已成为寻求针对包括癌症在内的各种复杂疾病的新型治疗干预措施的关键靶标。 FDA 批准的药物的重新定位为快速发现潜在的 HDAC3 抑制剂提供了一条有希望的途径。在这项研究中，我们对从 DrugBank 获得的 FDA 批准的药物进行了基于结构的虚拟筛选。候选命中是根据它们的结合亲和力以及与 HDAC3 的相互作用来选择的。然后对这些有前景的热门药物的生物特性和药物概况进行全面评估。我们的研究确定了两种 FDA 批准的药物：伊马替尼和卡匹帕明，其特点是对 HDAC3 结合袋具有卓越的亲和力和特异性。这些分子表现出对 HDAC3 结合位点的强烈偏好，并与活性位点口袋内具有功能意义的残基形成相互作用。为了更深入地了解结合动力学、结构稳定性和相互作用机制，我们进行了 300 纳秒 (ns) 的分子动力学 (MD) 模拟。 MD模拟结果表明，伊马替尼和卡匹帕明稳定了HDAC3的结构并诱导较少的构象变化。总而言之，这项研究的结果表明，伊马替尼和卡匹帕明可能为治疗复杂疾病，特别是癌症提供显着的治疗潜力。版权所有 © 2024 Shamsi、Khan、Yadav 和 Shahwan。

Histone deacetylase 3 (HDAC3) is a member of the histone deacetylase family that has emerged as a crucial target in the quest for novel therapeutic interventions against various complex diseases, including cancer. The repositioning of FDA-approved drugs presents a promising avenue for the rapid discovery of potential HDAC3 inhibitors. In this study, we performed a structure-based virtual screening of FDA-approved drugs obtained from DrugBank. Candidate hits were selected based on their binding affinities and interactions with HDAC3. These promising hits were then subjected to a comprehensive assessment of their biological properties and drug profiles. Our investigation identified two FDA-approved drugs, Imatinib and Carpipramine, characterized by their exceptional affinity and specificity for the binding pocket of HDAC3. These molecules demonstrated a strong preference for HDAC3 binding site and formed interactions with functionally significant residues within the active site pocket. To gain deeper insights into the binding dynamics, structural stability, and interaction mechanisms, we performed molecular dynamics (MD) simulations spanning 300 nanoseconds (ns). The results of MD simulations indicated that Imatinib and Carpipramine stabilized the structure of HDAC3 and induced fewer conformational changes. Taken together, the findings from this study suggest that Imatinib and Carpipramine may offer significant therapeutic potential for treating complex diseases, especially cancer.Copyright © 2024 Shamsi, Khan, Yadav and Shahwan.