ArticleProceedings of the National Academy of Sciences of the United States of America1999
Mimicry of erythropoietin by a nonpeptide molecule.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 103 citations in OpenAlex.
- Discovery and Characterization of Nonpeptidyl Agonists of the Tissue-Protective Erythropoietin Receptor.Molecular pharmacology · 2015Article
- Conserved nematode signalling molecules elicit plant defenses and pathogen resistance.Nature communications · 2015Article
- Erythropoietin use and abuse.Indian journal of endocrinology and metabolism · 2012Article
- Computer applications for prediction of protein-protein interactions and rational drug design.Advances and applications in bioinformatics and chemistry : AABC · 2009Article
- Erythropoietin: physiology and molecular mechanisms.Heart failure reviews · 2008Review
- Ligand discovery and virtual screening using the program LIDAEUS.British journal of pharmacology · 2008Review
- An integrative in silico approach for discovering candidates for drug-targetable protein-protein interactions in interactome data.BMC pharmacology · 2007Article
- Article
- Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era.Sports medicine (Auckland, N.Z.) · 2005Review
- A low molecular weight mimic of the Toll/IL-1 receptor/resistance domain inhibits IL-1 receptor-mediated responses.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- NMR characterization of interleukin-2 in complexes with the IL-2Ralpha receptor component, and with low molecular weight compounds that inhibit the IL-2/IL-Ralpha interaction.Protein science : a publication of the Protein Society · 2003Article
- Peptides identify multiple hotspots within the ligand binding domain of the TNF receptor 2.Proteome science · 2003Article
- Drugs for increasing oxygen and their potential use in doping: a review.Sports medicine (Auckland, N.Z.) · 2003Review
- Receptor recognition by gp130 cytokines.The EMBO journal · 2000Review
- Transgenic animal bioreactors.Transgenic research · 2000Review
- Understanding cytokine and growth factor receptor activation mechanisms.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythropoietin (EPO) controls the proliferation and differentiation of erythroid progenitor cells into red blood cells. EPO induces these effects by dimerization of the EPO receptors (EPOR) present on these cells. To discover nonpeptide molecules capable of mimicking the effects of EPO, we identified a small molecule capable of binding to one chain of EPOR and used it to synthesize molecules capable of inducing dimerization of the EPOR. We first identified compound 1 (N-3-[2-(4-biphenyl)-6-chloro-5-methyl]indolyl-acetyl-L-lysine methyl ester) by screening the in-house chemical collection for inhibitors of EPO binding to human EPOR and then prepared compound 5, which contains eight copies of compound 1 held together by a central core. Although both compounds inhibited EPO binding of EPOR, only compound 5 induced dimerization of soluble EPOR. Binding of EPO to its receptor in cells results in activation of many intracellular signaling molecules, including transcription factors like signal transducer and activator of transcription (STAT) proteins, leading to growth and differentiation of these cells. Consistent with its ability to induce dimerization of EPOR in solution, compound 5 exhibited much of the same biological activities as EPO, such as (i) the activation of a STAT-dependent luciferase reporter gene in BAF3 cells expressing human EPOR, (ii) supporting the proliferation of several tumor cell lines expressing the human or mouse EPOR, and (iii) the in vitro differentiation of human progenitor cells into colonies of erythrocytic lineage. These data demonstrate that a nonpeptide molecule is capable of inducing EPOR dimerization and mimicking the biological activities of EPO.
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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.