ArticleEuropean journal of medicinal chemistry2015
Design, synthesis and evaluation of marinopyrrole derivatives as selective inhibitors of Mcl-1 binding to pro-apoptotic Bim and dual Mcl-1/Bcl-xL inhibitors.
Article in European journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- Cancer Cell Cytotoxicity of Marinopyrroles, Pyrrolomycins, and Their Derivatives.Marine drugs · 2025Review
- Targeted Penetrating Motif Engineering of BH3 Mimetic: Harnessing Non-Canonical Amino Acids for Coinhibition of MCL-1 and BCL-xL in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Marinopyrrole derivative MP1 as a novel anti-cancer agent in group 3 MYC-amplified Medulloblastoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Analogs of Marinopyrrole A Show Enhancement to ObservedAntimicrobial agents and chemotherapy · 2022Article
- Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it.Exploration of targeted anti-tumor therapy · 2022Review
- Targeting MCL-1 in hematologic malignancies: Rationale and progress.Blood reviews · 2020Review
- Effects of novel pyrrolomycin MP1 in MYCN amplified chemoresistant neuroblastoma cell lines alone and combined with temsirolimus.BMC cancer · 2019Article
- BCL-2 Protein Family Interaction Analysis by Nuclear Magnetic Resonance Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma.International journal of molecular sciences · 2017Review
- Small-Molecule and Peptide Inhibitors of the Pro-Survival Protein Mcl-1.ChemMedChem · 2016Review
- New dimension in therapeutic targeting of BCL-2 family proteins.Oncotarget · 2015Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Inhibition of anti-apoptotic Mcl-1 is a promising anticancer strategy to overcome the survival and chemoresistance of a broad spectrum of human cancers. We previously reported on the identification of a natural product marinopyrrole A (1) that induces apoptosis in Mcl-1-dependent cells through Mcl-1 degradation. Here, we report the design and synthesis of novel marinopyrrole-based analogs and their evaluation as selective inhibitors of Mcl-1 as well as dual Mcl-1/Bcl-xL inhibitors. The most selective Mcl-1 antagonists were 34, 36 and 37 with 16-, 13- and 9-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding, respectively. Among the most potent dual inhibitors is 42 which inhibited Mcl-1/Bim and Bcl-xL/Bim binding 15-fold (IC50 = 600 nM) and 33-fold (500 nM) more potently than (±)-marinopyrrole A (1), respectively. Fluorescence quenching, NMR analysis and molecular docking indicated binding of marinopyrroles to the BH3 binding site of Mcl-1. Several marinopyrroles potently decreased Mcl-1 cellular levels and induced caspase 3 activation in human breast cancer cells. Our studies provide novel "lead" marinopyrroles for further optimization as selective Mcl-1 inhibitors and dual Mcl-1 and Bcl-xL inhibitors.
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