ArticleThe Journal of biological chemistry2013
LY2228820 dimesylate, a selective inhibitor of p38 mitogen-activated protein kinase, reduces angiogenic endothelial cord formation in vitro and in vivo.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- The functional role of p38 MAPK pathway in malignant brain tumors.Frontiers in pharmacology · 2022Review
- Strategies for Improving Photodynamic Therapy Through Pharmacological Modulation of the Immediate Early Stress Response.Methods in molecular biology (Clifton, N.J.) · 2022Review
- The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer.International journal of molecular sciences · 2021Review
- Design, Synthesis, and Structure-Activity Relationship Study of Potent MAPK11 Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- PD-L1 tumor-intrinsic signaling and its therapeutic implication in triple-negative breast cancer.JCI insight · 2021Article
- A Novel Small Peptide H-KI20 Inhibits Retinal Neovascularization Through the JNK/ATF2 Signaling Pathway.Investigative ophthalmology & visual science · 2021Article
- Novel Pathways for Targeting Tumor Angiogenesis in Metastatic Breast Cancer.Frontiers in oncology · 2021Review
- Xinkeshu Improves Endothelial Function and Augments Reendothelialization Capacity in Coronary Artery Disease with Anxiety/Depression.Oxidative medicine and cellular longevity · 2021Article
- Blockade of p38 kinase impedes the mobilization of protumorigenic myeloid populations to impact breast cancer metastasis.International journal of cancer · 2020Article
- APOE2 promotes the development and progression of subretinal neovascularization in age-related macular degeneration via MAPKs signaling pathway.Saudi journal of biological sciences · 2020Article
- A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.Genome biology · 2020Article
- Edoxaban improves atrial fibrillation and thromboembolism through regulation of the Wnt-β-induced PI3K/ATK-activated protein C system.Experimental and therapeutic medicine · 2019Article
- The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical manner.Life science alliance · 2019Article
- Glioblastoma endothelium drives bevacizumab-induced infiltrative growth via modulation of PLXDC1.International journal of cancer · 2019Article
- LY2228820 induces synergistic anti-cancer effects with anti-microtubule chemotherapeutic agents independent of P-glycoprotein in multidrug resistant cancer cells.American journal of cancer research · 2019Article
- Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer.Investigational new drugs · 2018Article
- Tumor p38MAPK signaling enhances breast carcinoma vascularization and growth by promoting expression and deposition of pro-tumorigenic factors.Oncotarget · 2017Article
- The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells.Oncotarget · 2017Review
- LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer.Oncotarget · 2017Article
- Oncogenic Ras modulates p38 MAPK-mediated inflammatory cytokine production in glioblastoma cells.Cancer biology & therapy · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LY2228820 dimesylate is a highly selective small molecule inhibitor of p38α and p38β mitogen-activated protein kinases (MAPKs) that is currently under clinical investigation for human malignancies. p38 MAPK is implicated in a wide range of biological processes, in particular those that support tumorigenesis. One such process, angiogenesis, is required for tumor growth and metastasis, and many new cancer therapies are therefore directed against the tumor vasculature. Using an in vitro co-culture endothelial cord formation assay, a surrogate of angiogenesis, we investigated the role of p38 MAPK in growth factor- and tumor-driven angiogenesis using LY2228820 dimesylate treatment and by shRNA gene knockdown. p38 MAPK was activated in endothelial cells upon growth factor stimulation, with inhibition by LY2228820 dimesylate treatment causing a significant decrease in VEGF-, bFGF-, EGF-, and IL-6-induced endothelial cord formation and an even more dramatic decrease in tumor-driven cord formation. In addition to involvement in downstream cytokine signaling, p38 MAPK was important for VEGF, bFGF, EGF, IL-6, and other proangiogenic cytokine secretion in stromal and tumor cells. LY2228820 dimesylate results were substantiated using p38α MAPK-specific shRNA and shRNA against the downstream p38 MAPK effectors MAPKAPK-2 and HSP27. Using in vivo models of functional neoangiogenesis, LY2228820 dimesylate treatment reduced hemoglobin content in a plug assay and decreased VEGF-A-stimulated vascularization in a mouse ear model. Thus, p38α MAPK is implicated in tumor angiogenesis through direct tumoral effects and through reduction of proangiogenic cytokine secretion via the microenvironment.
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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.