ArticleCancer research2016
Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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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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
22 citing papers in PubMed, 45 citations in OpenAlex.
- A high-sensitivity TIE2-GRB2 BRET platform for functional and pharmacologic profiling of pathogenic variants associated with venous malformations.Angiogenesis · 2026Article
- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- Targeting Neuroinflammation and Cognitive Decline: First-in-Class Dual Butyrylcholinesterase and p38α Mitogen-Activated Protein Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells.Archiv der Pharmazie · 2025Article
- Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- The Importance of the Pyrazole Scaffold in the Design of Protein Kinases Inhibitors as Targeted Anticancer Therapies.Molecules (Basel, Switzerland) · 2023Review
- Role of protein phosphorylation in cell signaling, disease, and the intervention therapy.MedComm · 2022Review
- Megakaryopoiesis impairment through acute innate immune signaling activation by azacitidine.The Journal of experimental medicine · 2022Article
- Pexmetinib suppresses osteoclast formation and breast cancer induced osteolysis via P38/STAT3 signal pathway.Journal of bone oncology · 2022Article
- Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma.International journal of molecular sciences · 2022Review
- Methylation of dual-specificity phosphatase 4 controls cell differentiation.Cell reports · 2021Article
- Stem Cells in the Myelodysplastic Syndromes.Frontiers in aging · 2021Review
- miR-497 plays a key role in Tanshinone IIA-attenuated proliferation in OCI-AML3 cells via the MAPK/ERK1/2 pathway.Cytotechnology · 2020Article
- Tetraspanin CD82 drives acute myeloid leukemia chemoresistance by modulating protein kinase C alpha and β1 integrin activation.Oncogene · 2020Article
- An overview of mammalian p38 mitogen-activated protein kinases, central regulators of cell stress and receptor signaling.F1000Research · 2020Review
- Small molecule purine and pseudopurine derivatives: synthesis, cytostatic evaluations and investigation of growth inhibitory effect in non-small cell lung cancer A549.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Disordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes.Current hematologic malignancy reports · 2018Review
- Targeting Nicotinamide N-Methyltransferase and miR-449a in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer Cells.Molecular therapy. Nucleic acids · 2018Article
- Ulva pertusa lectin 1 delivery through adenovirus vector affects multiple signaling pathways in cancer cells.Glycoconjugate journal · 2017Article
Corrections and comments
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Authors and funding
36 authors at 1 institution in 1 country.
Funding
Abstract
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) suppress normal hematopoietic activity in part by enabling a pathogenic inflammatory milieu in the bone marrow. In this report, we show that elevation of angiopoietin-1 in myelodysplastic CD34(+) stem-like cells is associated with higher risk disease and reduced overall survival in MDS and AML patients. Increased angiopoietin-1 expression was associated with a transcriptomic signature similar to known MDS/AML stem-like cell profiles. In seeking a small-molecule inhibitor of this pathway, we discovered and validated pexmetinib (ARRY-614), an inhibitor of the angiopoietin-1 receptor Tie-2, which was also found to inhibit the proinflammatory kinase p38 MAPK (which is overactivated in MDS). Pexmetinib inhibited leukemic proliferation, prevented activation of downstream effector kinases, and abrogated the effects of TNFα on healthy hematopoietic stem cells. Notably, treatment of primary MDS specimens with this compound stimulated hematopoiesis. Our results provide preclinical proof of concept for pexmetinib as a Tie-2/p38 MAPK dual inhibitor applicable to the treatment of MDS/AML. Cancer Res; 76(16); 4841-9. ©2016 AACR.
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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.