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MCL-1作为癌症的有效靶点:最新进展、结构见解及构效关系研究

MCL-1 as a potent target for cancer: Recent advancements, structural insights and SAR studies.

作者信息

Sharma Vishakha, Kumar Ankush

机构信息

Amity School of Pharmaceutical Sciences, Amity University Punjab, Mohali, India.

Amity School of Pharmaceutical Sciences, Amity University Punjab, Mohali, India.

出版信息

Bioorg Chem. 2025 Mar;156:108211. doi: 10.1016/j.bioorg.2025.108211. Epub 2025 Jan 27.

Abstract

The myeloid cell leukemia-1 (Mcl-1) differentiation protein belongs to the B-cell lymphoma 2 (Bcl-2) family of proteins which regulates the apoptosis or cell death. Mcl-1 is known for its pro-survival in response to various stressors. Therefore, it acts as a prominent target in cancer treatment. Mcl-1 has emerged as one of the validated drug targets for anticancer drug discovery as their expression has been implicated in the pathogenesis of cancers. In this review, we have included the various inhibitors based on many heterocyclic rings such as pyrrole, pyrazole, coumarin, quinoline and indole. This manuscript incorporates the anticancer activity, structure activity relationship (SAR) and molecular modelling of recently synthesized Mcl-1 inhibitors. The clinical trial status of Mcl-1 inhibitors is also described. But till now, no Mcl-1 inhibitor has been approved by any drug authority. This review is based on extensive research in the field of designing Mcl-1 inhibitors from 2020 to till now. It will provide extensive information to researchers and scientists for designing of novel Mcl-1 inhibitors.

摘要

髓样细胞白血病-1(Mcl-1)分化蛋白属于调节细胞凋亡或细胞死亡的B细胞淋巴瘤2(Bcl-2)蛋白家族。Mcl-1以其在应对各种应激源时的促生存作用而闻名。因此,它成为癌症治疗中的一个重要靶点。Mcl-1已成为经证实的抗癌药物发现靶点之一,因为其表达与癌症发病机制有关。在本综述中,我们纳入了基于许多杂环如吡咯、吡唑、香豆素、喹啉和吲哚的各种抑制剂。本文阐述了最近合成的Mcl-1抑制剂的抗癌活性、构效关系(SAR)和分子模拟。还描述了Mcl-1抑制剂的临床试验状况。但到目前为止,尚无Mcl-1抑制剂获得任何药物管理机构的批准。本综述基于2020年至今在设计Mcl-1抑制剂领域的广泛研究。它将为研究人员和科学家设计新型Mcl-1抑制剂提供广泛信息。

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