ArticleOncotarget2015
Maritoclax and dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Broad-Spectrum Anti-Infective Activity of Natural Compounds Pyrrolomycins, Marinopyrroles, and Their Analogs.Pathogens (Basel, Switzerland) · 2026Review
- Maritoclax Overcomes FBW7 Deficiency-Driven Irinotecan Resistance in Colorectal Cancer by Targeting MCL1.Cancer medicine · 2025Article
- Cancer Cell Cytotoxicity of Marinopyrroles, Pyrrolomycins, and Their Derivatives.Marine drugs · 2025Review
- Novel selective strategies targeting the BCL-2 family to enhance clinical efficacy in ALK-rearranged non-small cell lung cancer.Cell death & disease · 2025Article
- CDK9 inhibition as an effective therapy for small cell lung cancer.Cell death & disease · 2024Article
- Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy.Cell death discovery · 2022Article
- Non-coding RNA-related antitumor mechanisms of marine-derived agents.Frontiers in pharmacology · 2022Review
- Learning from Nature: From a Marine Natural Product to Synthetic Cyclooxygenase-1 Inhibitors by Automated De Novo Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Article
- Targeting MCL-1 in hematologic malignancies: Rationale and progress.Blood reviews · 2020Review
- Single Agent and Synergistic Activity of Maritoclax with ABT-263 in Nasopharyngeal Carcinoma (NPC) Cell Lines.Tropical life sciences research · 2020Article
- Targeting intermediary metabolism enhances the efficacy of BH3 mimetic therapy in hematologic malignancies.Haematologica · 2019Article
- The Role of Inhibition of Apoptosis in Acute Leukemias and Myelodysplastic Syndrome.Frontiers in oncology · 2019Review
- DRP-1 functions independently of mitochondrial structural perturbations to facilitate BH3 mimetic-mediated apoptosis.Cell death discovery · 2019Article
- Article
- Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells.The Journal of clinical investigation · 2018Article
- Maritoclax Enhances TRAIL-Induced Apoptosis via CHOP-Mediated Upregulation of DR5 and miR-708-Mediated Downregulation of cFLIP.Molecules (Basel, Switzerland) · 2018Article
- Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor suppression.The Journal of clinical investigation · 2018Article
- Pathways and mechanisms of venetoclax resistance.Leukemia & lymphoma · 2017Review
- DRP-1 is required for BH3 mimetic-mediated mitochondrial fragmentation and apoptosis.Cell death & disease · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The anti-apoptotic BCL-2 family proteins are important targets for cancer chemotherapy. Specific and potent inhibitors of the BCL-2 family, such as ABT-263 (navitoclax) and ABT-199, are only effective against some members of the BCL-2 family but do not target MCL-1, which is commonly amplified in tumors and associated with chemoresistance. In this report, the selectivity and potency of two putative MCL-1 inhibitors, dinaciclib and maritoclax, were assessed. Although both compounds induced Bax/Bak- and caspase-9-dependent apoptosis, dinaciclib was more potent than maritoclax in downregulating MCL-1 and also in inducing apoptosis. However, the compounds induced apoptosis, even in cells lacking MCL-1, suggesting multiple mechanisms of cell death. Furthermore, maritoclax induced extensive mitochondrial fragmentation, and a Bax/Bak- but MCL-1-independent accumulation of mitochondrial reactive oxygen species (ROS), with an accompanying loss of complexes I and III of the electron transport chain. ROS scavengers, such as MitoQ, could not salvage maritoclax-mediated effects on mitochondrial structure and function. Taken together, our data demonstrate that neither dinaciclib nor maritoclax exclusively target MCL-1. Although dinaciclib is clearly not a specific MCL-1 inhibitor, its ability to rapidly downregulate MCL-1 may be beneficial in many clinical settings, where it may reverse chemoresistance or sensitize to other chemotherapeutic agents.
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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.