Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Humdard University, New Delhi, India.
Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
Med Oncol. 2023 Jun 9;40(7):201. doi: 10.1007/s12032-023-02058-x.
Recent studies highlight the great potential impact of HDAC inhibitors (HDACis) in suppressing TNBC, even though clinical trials including a single HDACis demonstrated unsatisfactory outcomes against TNBC. New compounds created to achieve isoform selectivity and/or a polypharmacological HDAC strategy have also produced interesting results. The current study discusses the HDACis pharmacophoric models and the structural alterations that produced drugs with strong inhibitory effects on TNBC progression. With more than 2 million new cases reported in 2018, breast cancer-the most common cancer among women worldwide-poses a significant financial burden on an already deteriorating public health system. Due to a lack of therapies being developed for triple-negative breast cancers and the development of resistance to the current treatment options, it is imperative to plan novel therapeutics in order to bring new medications to the pipeline. Additionally, HDACs deacetylate a large number of nonhistone cellular substrates that control a variety of biological processes, such as the beginning and development of cancer. The significance of HDACs in cancer and the therapeutic potential of HDAC inhibitor. Furthermore, we also reported molecular docking study with four HDAC inhibitors and performed molecular dynamic stimulation of the best dock score compound. Among the four ligands belinostat compound showed best binding affinity with histone deacetylase protein which was -8.7 kJ/mol. It also formed five conventional hydrogen bond with Gly 841, His 669, His 670, pro 809, and His 709 amino acid residues.
最近的研究强调了 HDAC 抑制剂 (HDACi) 在抑制三阴性乳腺癌方面的巨大潜在影响,尽管包括单一 HDACi 在内的临床试验对三阴性乳腺癌的疗效并不令人满意。为了实现同工酶选择性和/或多效性 HDAC 策略而创建的新化合物也产生了有趣的结果。本研究讨论了 HDACi 的药效团模型和结构改变,这些改变产生了对三阴性乳腺癌进展具有强抑制作用的药物。2018 年报告了超过 200 万例新病例,乳腺癌——全球女性最常见的癌症——对已经恶化的公共卫生系统造成了巨大的经济负担。由于缺乏针对三阴性乳腺癌的治疗方法以及对现有治疗方案的耐药性发展,迫切需要制定新的治疗方法,以便将新药物推向研发管线。此外,HDAC 去乙酰化大量非组蛋白细胞底物,这些底物控制着多种生物过程,如癌症的起始和发展。HDAC 在癌症中的重要性和 HDAC 抑制剂的治疗潜力。此外,我们还报告了对四种 HDAC 抑制剂的分子对接研究,并对最佳对接评分化合物进行了分子动力学刺激。在这四种配体中,贝林司他化合物与组蛋白去乙酰化酶蛋白的结合亲和力最好,为-8.7 kJ/mol。它还与 Gly 841、His 669、His 670、pro 809 和 His 709 氨基酸残基形成了五个常规氢键。