ArticleJournal of medicinal chemistry2016
Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
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Who cites it
46 citing papers in PubMed.
- Proteolysis Targeting Chimera (PROTAC) Linkerology Enhances the CDK-Degradation Selectivity Profile of a Multi-CDK Inhibitor: Discovery of Potent, Anti-Leukemic CDK9 Degraders.ACS pharmacology & translational science · 2026Article
- Network pharmacology and molecular modelling analysis ofFrontiers in bioinformatics · 2026Article
- Discovery of Macrocyclic Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors that Demonstrate Potent Cellular Efficacy and In Vivo Activity in a Mouse Solid Tumor Xenograft Model.Journal of medicinal chemistry · 2025Article
- Siloxane-spaced salen-type Schiff base cobalt complex. Experimental and docking analysis-a dual approach for evaluating anti-cancer efficacy.Royal Society open science · 2025Article
- Augmenting the Anti-Leukemic Activity of the BCL-2 Inhibitor Venetoclax Through Its Transformation Into Polypharmacologic Dual BCL-2/HDAC1 and Dual BCL-2/HDAC6 Inhibitors.Drug development research · 2025Article
- Drugging Challenging Cancer Targets Using Fragment-Based Methods.Chemical reviews · 2025Review
- Apoptotic Potential of Iloneoside from Gongronema latifolium Benth against Prostate Cancer Cells Using In Vitro and In Silico Approach.Cell biochemistry and biophysics · 2025Article
- Discovery of a Myeloid Cell Leukemia 1 (Mcl-1) Inhibitor That Demonstrates PotentJournal of medicinal chemistry · 2024Article
- Design and synthesis of Meldrum's acid based 7-azaindole anchored 1,2,3-triazole hybrids as anticancer agents.RSC medicinal chemistry · 2024Article
- Natural 2',4-Dihydroxy-4',6'-dimethoxy Chalcone Isolated fromPlants (Basel, Switzerland) · 2024Article
- Tetrazole and acylsulfonamide bioisosteric replacements of the carboxylic acid in a dual MCL-1/BCL-xRSC advances · 2023Article
- A Novel Tri-Hydroxy-Methylated Chalcone Isolated fromInternational journal of molecular sciences · 2023Article
- Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach.Journal of medicinal chemistry · 2023Article
- Discovery ofRSC medicinal chemistry · 2023Article
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- In vitro and in silico studies for the identification of anti-cancer and antibacterial peptides from camel milk protein hydrolysates.PloS one · 2023Article
- Molecular docking analysis of MCL-1 inhibitors for breast cancer management.Bioinformation · 2023Article
- Patent landscape of inhibitors and PROTACs of the anti-apoptotic BCL-2 family proteins.Expert opinion on therapeutic patents · 2022Review
- Scaffold hopping from indoles to indazoles yields dual MCL-1/BCL-2 inhibitors from MCL-1 selective leads.RSC medicinal chemistry · 2022Article
- Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer.Biochemical Society transactions · 2021Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins responsible for the regulation of programmed cell death. Amplification of Mcl-1 is a common genetic aberration in human cancer whose overexpression contributes to the evasion of apoptosis and is one of the major resistance mechanisms for many chemotherapies. Mcl-1 mediates its effects primarily through interactions with pro-apoptotic BH3 containing proteins that achieve high affinity for the target by utilizing four hydrophobic pockets in its binding groove. Here we describe the discovery of Mcl-1 inhibitors using fragment-based methods and structure-based design. These novel inhibitors exhibit low nanomolar binding affinities to Mcl-1 and >500-fold selectivity over Bcl-xL. X-ray structures of lead Mcl-1 inhibitors when complexed to Mcl-1 provided detailed information on how these small-molecules bind to the target and were used extensively to guide compound optimization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.