ArticleOncotarget2015
Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Comprehensive exploration of JQ1 and GSK2801 targets in breast cancer using network pharmacology and molecular modeling approaches.Computational and structural biotechnology journal · 2023Article
- CDK9 inhibitors in multiple myeloma: a review of progress and perspectives.Medical oncology (Northwood, London, England) · 2022Review
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
- Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.Blood advances · 2021Article
- Review
- Future of Personalized Therapy Targeting Aberrant Signaling Pathways in Multiple Myeloma.Clinical lymphoma, myeloma & leukemia · 2019Review
- The BET Bromodomain Inhibitor I-BET-151 Induces Structural and Functional Alterations of the Heart Mitochondria in Healthy Male Mice and Rats.International journal of molecular sciences · 2019Article
- Epigenetic-Based Mechanisms of Osteoblast Suppression in Multiple Myeloma Bone Disease.JBMR plus · 2019Review
- The Bromodomain Inhibitor JQ1 Enhances the Responses to All-International journal of stem cells · 2018Article
- Article
- Article
- Functional relevance of in vivo half antibody exchange of an IgG4 therapeutic antibody-drug conjugate.PloS one · 2018Article
- 1,2,3,4,6-Penta-Frontiers in pharmacology · 2018Article
- Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mitochondrial pathway.Oncotarget · 2017Article
- The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity inHaematologica · 2017Article
- BET bromodomain inhibitors synergize with ATR inhibitors in melanoma.Cell death & disease · 2017Article
- Review
- Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.Oncotarget · 2017Article
- A Novel Epi-drug Therapy Based on the Suppression of BET Family Epigenetic Readers.The Yale journal of biology and medicine · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
purposeDespite significant therapeutic progress in multiple myeloma, drug resistance is uniformly inevitable and new treatments are needed. Our aim was to identify novel, efficacious small-molecule combinations for use in drug resistant multiple myeloma. EXPERIMENTAL
designA panel of 116 small molecule inhibitors was used to screen resistant myeloma cell lines for potential therapeutic targets. Agents found to have enhanced activity in the bortezomib or melphalan resistant myeloma cell lines were investigated further in combination. Synergistic combinations of interest were evaluated in primary patient cells.
resultsThe overall single-agent drug sensitivity profiles were dramatically different between melphalan and bortezomib resistant cells, however, the bromodomain inhibitor, CPI203, was observed to have enhanced activity in both the bortezomib and melphalan resistant lines compared to their wild-type counterparts. The combination of bortezomib and CPI203 was found to be synergistic in both the bortezomib and melphalan resistant cell lines as well as in a primary multiple myeloma sample from a patient refractory to recent proteasome inhibitor treatment. The CPI203-bortezomib combination led to enhanced apoptosis and anti-proliferative effects. Finally, in contrast to prior reports of synergy between bortezomib and other epigenetic modifying agents, which implicated MYC downregulation or NOXA induction, our analyses suggest that CPI203-bortezomib synergy is independent of these events.
conclusionOur preclinical data supports a role for the clinical investigation of the bromodomain inhibitor CPI203 combined with bortezomib or alkylating agents in resistant multiple myeloma.
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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.