ArticleJournal of medicinal chemistry2015
Discovery of tricyclic indoles that potently inhibit Mcl-1 using fragment-based methods and structure-based design.
Article in 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 19 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- 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
- Drugging Challenging Cancer Targets Using Fragment-Based Methods.Chemical reviews · 2025Review
- Discovery of a Myeloid Cell Leukemia 1 (Mcl-1) Inhibitor That Demonstrates PotentJournal of medicinal chemistry · 2024Article
- Synthesis of Functionalized 3Molecules (Basel, Switzerland) · 2023Article
- Discovery ofRSC medicinal chemistry · 2023Article
- Targeting MCL-1 in cancer: current status and perspectives.Journal of hematology & oncology · 2021Review
- Discovery and Characterization of 2,5-Substituted Benzoic Acid Dual Inhibitors of the Anti-apoptotic Mcl-1 and Bfl-1 Proteins.Journal of medicinal chemistry · 2020Article
- The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells.eLife · 2019Article
- Peptide-Directed Binding for the Discovery of Modulators of α-Helix-Mediated Protein-Protein Interactions: Proof-of-Concept Studies with the Apoptosis Regulator Mcl-1.Angewandte Chemie (International ed. in English) · 2017Article
- Article
- Structure of a Myeloid cell leukemia-1 (Mcl-1) inhibitor bound to drug site 3 of Human Serum Albumin.Bioorganic & medicinal chemistry · 2017Article
- From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors.Nature reviews. Drug discovery · 2017Review
- Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors.ACS medicinal chemistry letters · 2017Article
- Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors.FEBS letters · 2017Article
- Twenty years on: the impact of fragments on drug discovery.Nature reviews. Drug discovery · 2016Review
- Allosteric inhibition of antiapoptotic MCL-1.Nature structural & molecular biology · 2016Article
- Rapid Optimization of Mcl-1 Inhibitors using Stapled Peptide Libraries Including Non-Natural Side Chains.ACS chemical biology · 2016Article
- Article
- Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods.Journal of medicinal chemistry · 2016Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that is overexpressed and amplified in many cancers. Overexpression of Mcl-1 allows cancer cells to evade apoptosis and contributes to the resistance of cancer cells to be effectively treated with various chemotherapies. From an NMR-based screen of a large fragment library, several distinct chemical scaffolds that bind to Mcl-1 were discovered. Here, we describe the discovery of potent tricyclic 2-indole carboxylic acid inhibitors that exhibit single digit nanomolar binding affinity to Mcl-1 and greater than 1700-fold selectivity over Bcl-xL and greater than 100-fold selectivity over Bcl-2. X-ray structures of these compounds when complexed to Mcl-1 provide detailed information on how these small-molecules bind to the target, which was used 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.