ArticleCell death & disease2015
Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax).
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 247 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
247 citing papers in PubMed, 1 synthesis or guideline pooled it, 427 citations in OpenAlex.
- Top 100 most-cited articles on apoptosis of non-small cell lung cancer over the past two decades: a bibliometrics analysis.Frontiers in immunology · 2024Pooled it
- A Phase I/II Trial of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- PI3Kδ inhibitor YY‑20394 is effective alone or in combination with Bcl‑2 inhibitor ABT199 in acute myeloid leukemia cells.Oncology reports · 2026Article
- Navitoclax-encapsulated dual pH-responsive copolymeric nanoparticles improves hepatocellular carcinoma treatment with induction of apoptosis and immune activation.Journal of nanobiotechnology · 2026Article
- Saga of MCL1 inhibitors in multiple myeloma.Biochemical pharmacology · 2026Review
- siRNA-Based Nanodrug Delivery Systems in the Treatment of Autoimmune Diseases.Journal of immunology research · 2026Review
- Boosting Drug Discovery: Expanding the Applicability of Fragment Dissolved Molecular Dynamics to Accelerate Binding Mode Elucidation.Journal of chemical information and modeling · 2025Article
- Cancer Cell Cytotoxicity of Marinopyrroles, Pyrrolomycins, and Their Derivatives.Marine drugs · 2025Review
- Effect of Selenium Fortification on Growth Performance and Nutritional Compounds of Kale (Foods (Basel, Switzerland) · 2025Article
- 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
- Review
- Computational design of potent and selective binders of BAK and BAX.Science advances · 2025Article
- Review
- BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress.Nature communications · 2025Article
- Pioneering the Battle Against Breast Cancer: The Promise of New Bcl-2 Family.Anti-cancer agents in medicinal chemistry · 2025Review
- Flow cytometric expression of Bcl-2, Mcl-1, and their ratios correlates with primary and secondary cytogenetic changes and their combinations in multiple myeloma.Annals of hematology · 2024Article
- Synthesis, Anti-Cancer Activity, Cell Cycle Arrest, Apoptosis Induction, and Docking Study of Fused Benzo[Molecules (Basel, Switzerland) · 2024Article
- Low BCL-xL expression in triple-negative breast cancer cells favors chemotherapy efficacy, and this effect is limited by cancer-associated fibroblasts.Scientific reports · 2024Article
- Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1.Journal of medicinal chemistry · 2024Article
- Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.Molecular cell · 2024Article
187 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
28 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein-protein interactions, and therefore designing small molecules potent enough to inhibit MCL-1 in cells has proven extremely challenging. Here, we describe a series of indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to MCL-1 selectively and with sufficient affinity to disrupt MCL-1-BIM complexes in living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-XL inhibitor navitoclax to kill a variety of cancer cell lines. This work represents the first description of small-molecule MCL-1 inhibitors with sufficient potency to induce clear on-target cellular activity. It also demonstrates the utility of these molecules as chemical tools for dissecting the basic biology of MCL-1 and the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the treatment of cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.