ArticleOncogene2002
UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 63 citations in OpenAlex.
- Sam68 is a druggable vulnerability point in cancer stem cells.Cancer metastasis reviews · 2024Review
- Development of small-molecule Tau-SH3 interaction inhibitors that prevent amyloid-β toxicity and network hyperexcitability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.Oncogene · 2023Review
- Review
- Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022Review
- Article
- A Luminacin D Analog HL142 Inhibits Ovarian Tumor Growth and Metastasis by Reversing EMT and Attenuating the TGFβ and FAK Pathways.Journal of Cancer · 2021Article
- SOS1 interacts with Grb2 through regions that induce closed nSH3 conformations.The Journal of chemical physics · 2020Article
- High-Affinity Interactions of the nSH3/cSH3 Domains of Grb2 with the C-Terminal Proline-Rich Domain of SOS1.Journal of the American Chemical Society · 2020Article
- Molecular Dynamics model of peptide-protein conjugation: case study of covalent complex between Sos1 peptide and N-terminal SH3 domain from Grb2.Scientific reports · 2019Article
- Aminoquinoline-Rhodium(II) Conjugates as Src-Family SH3 Ligands.ACS medicinal chemistry letters · 2019Article
- PEPD is a pivotal regulator of p53 tumor suppressor.Nature communications · 2017Article
- Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors.Chemical science · 2015Article
- Inhibition of IGF-1-Mediated Cellular Migration and Invasion by Migracin A in Ovarian Clear Cell Carcinoma Cells.PloS one · 2015Article
- Small molecule inhibitors of the HIV-1 virulence factor, Nef.Drug discovery today. Technologies · 2013Review
- Mammalian son of sevenless Guanine nucleotide exchange factors: old concepts and new perspectives.Genes & cancer · 2011Article
- Grb2 signaling in cell motility and cancer.Expert opinion on therapeutic targets · 2008Review
- Targeting AMAP1 and cortactin binding bearing an atypical src homology 3/proline interface for prevention of breast cancer invasion and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- Comparative genomic assessment of novel broad-spectrum targets for antibacterial drugs.Comparative and functional genomics · 2004Article
- Tr-kit promotes the formation of a multimolecular complex composed by Fyn, PLCgamma1 and Sam68.Oncogene · 2003Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein interactions play critical regulatory roles in mediating signal transduction. Previous studies have identified an unconventional, small-molecule, Src signal transduction inhibitor, UCS15A. UCS15A differed from conventional Src-inhibitors in that it did not alter the levels or the tyrosine kinase activity of Src. Our studies suggested that UCS15A exerted its Src-inhibitory effects by a novel mechanism that involved the disruption of protein-protein interactions mediated by Src. In the present study we have examined the ability of UCS15A to disrupt the interaction of Src-SH3 with Sam68, both in vivo and in vitro. This ability of UCS15A was not restricted to Src-SH3 mediated protein-protein interactions, since the drug was capable of disrupting the in vivo interactions of Sam68 with other SH3 domain containing proteins such as Grb2 and PLCgamma. In addition, UCS15A was capable of disrupting other typical SH3-mediated protein-protein interactions such as Grb2-Sos1, cortactin-ZO1, as well as atypical SH3-mediated protein-protein interactions such as Grb2-Gab1. However, UCS15A was unable to disrupt the non-SH3-mediated protein-protein interactions of beta-catenin, with E-cadherin and alpha-catenin. In addition, UCS15A had no effect on the SH2-mediated interaction between Grb2 and activated Epidermal Growth Factor receptor. Thus, the ability of UCS15A, to disrupt protein-protein interactions appeared to be restricted to SH3-mediated protein-protein interactions. In this regard, UCS15A represents the first example of a non-peptide, small molecule agent capable of disrupting SH3-mediated protein-protein interactions. In vitro analyses suggested that UCS15A did not bind to the SH3 domain itself but rather may interact directly with the target proline-rich domains.
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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.