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- Publisher Website: 10.1016/j.chembiol.2017.01.003
- Scopus: eid_2-s2.0-85011296351
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Article: Small-Molecule Inhibitors of the SOX18 Transcription Factor
Title | Small-Molecule Inhibitors of the SOX18 Transcription Factor |
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Authors | |
Keywords | SOX transcription factor protein-DNA interaction small-molecule salicylate protein-protein interaction |
Issue Date | 2017 |
Citation | Cell Chemical Biology, 2017, v. 24, n. 3, p. 346-359 How to Cite? |
Abstract | © 2017 Elsevier Ltd Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors. We identified two compounds, which inspired a series of synthetic SOX18 inhibitors, able to interfere with the SOX18 HMG DNA-binding domain, and to disrupt HMG-dependent protein-protein interaction with RBPJ. These compounds also perturbed SOX18 transcriptional activity in a cell-based reporter gene system. This approach may prove useful in developing a new class of anti-angiogenic compounds based on the inhibition of TF activity. |
Persistent Identifier | http://hdl.handle.net/10722/253125 |
ISSN | 2023 Impact Factor: 6.6 2023 SCImago Journal Rankings: 2.584 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Fontaine, Frank | - |
dc.contributor.author | Overman, Jeroen | - |
dc.contributor.author | Moustaqil, Mehdi | - |
dc.contributor.author | Mamidyala, Sreeman | - |
dc.contributor.author | Salim, Angela | - |
dc.contributor.author | Narasimhan, Kamesh | - |
dc.contributor.author | Prokoph, Nina | - |
dc.contributor.author | Robertson, Avril A.B. | - |
dc.contributor.author | Lua, Linda | - |
dc.contributor.author | Alexandrov, Kirill | - |
dc.contributor.author | Koopman, Peter | - |
dc.contributor.author | Capon, Robert J. | - |
dc.contributor.author | Sierecki, Emma | - |
dc.contributor.author | Gambin, Yann | - |
dc.contributor.author | Jauch, Ralf | - |
dc.contributor.author | Cooper, Matthew A. | - |
dc.contributor.author | Zuegg, Johannes | - |
dc.contributor.author | Francois, Mathias | - |
dc.date.accessioned | 2018-05-11T05:38:40Z | - |
dc.date.available | 2018-05-11T05:38:40Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Cell Chemical Biology, 2017, v. 24, n. 3, p. 346-359 | - |
dc.identifier.issn | 2451-9456 | - |
dc.identifier.uri | http://hdl.handle.net/10722/253125 | - |
dc.description.abstract | © 2017 Elsevier Ltd Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors. We identified two compounds, which inspired a series of synthetic SOX18 inhibitors, able to interfere with the SOX18 HMG DNA-binding domain, and to disrupt HMG-dependent protein-protein interaction with RBPJ. These compounds also perturbed SOX18 transcriptional activity in a cell-based reporter gene system. This approach may prove useful in developing a new class of anti-angiogenic compounds based on the inhibition of TF activity. | - |
dc.language | eng | - |
dc.relation.ispartof | Cell Chemical Biology | - |
dc.subject | SOX transcription factor | - |
dc.subject | protein-DNA interaction | - |
dc.subject | small-molecule | - |
dc.subject | salicylate | - |
dc.subject | protein-protein interaction | - |
dc.title | Small-Molecule Inhibitors of the SOX18 Transcription Factor | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.chembiol.2017.01.003 | - |
dc.identifier.scopus | eid_2-s2.0-85011296351 | - |
dc.identifier.volume | 24 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 346 | - |
dc.identifier.epage | 359 | - |
dc.identifier.eissn | 2451-9448 | - |
dc.identifier.isi | WOS:000397424600012 | - |
dc.identifier.issnl | 2451-9448 | - |