The B-cell lymphoma protein 2 (Bcl-2) family functions as a tripartite switch for cell death, meticulously modulating the intrinsic apoptosis pathway in response to diverse cellular signaling stresses via protein-protein interactions. As a key and unique member, myeloid cell leukemia-1 (Mcl-1) is crucial for the regulation of mitochondrial function within the intrinsic apoptotic pathway. Mcl-1 is overexpressed in numerous hematological malignancies as well as solid tumors, closely associated to tumor development, unsatisfactory prognosis, and resistance to chemotherapy. Consequently, it represents a promising therapeutic target in cancer treatment. In 2018, we reviewed the advances of small-molecule Mcl-1 inhibitors from 2012 to 2017. This review aims to summarize the updated advances of small-molecule Mcl-1 inhibitors (according to their core scaffolds) or degraders as promising anti-cancer agents (2018-present). Furthermore, the corresponding structure-activity relationships (SARs) of most compounds are also provided. Additionally, the co-crystal structures of some potent compounds in complex with Mcl-1 protein are also elucidated. This review is expected to provide valuable insights for medicinal chemists engaged in developing more effective small-molecule inhibitors or degraders targeting Mcl-1.

2025-11-01·Trends in Cancer

Canonical and non-canonical intricacies of MCL-1 in cancer

Article

作者: Mittal, Pooja ; Lenz, Heinz-Josef

Myeloid cell leukemia 1 (MCL-1), an antiapoptotic protein, belongs to the BCL-2 protein family and is an extensively studied anticancer target. MCL-1 inhibitors have been in development for decades but fall short on efficacy, toxicity, and side-effects. Recently, Brinkmann et al. shed light on the apoptosis-unrelated function of MCL-1 and its physiological role that could critically lead to MCL-1 inhibitor development.

2025-03-01·BIOORGANIC CHEMISTRY

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

Review

作者: Sharma, Vishakha ; Kumar, Ankush

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.

100 项与 Mcl-1 inhibitors(Eutropics Pharmaceuticals) 相关的药物交易

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