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Pyrimidine-Based In...
Pyrimidine-Based Inhibitors of Dynamin I GTPase Activity : Competitive Inhibition at the Pleckstrin Homology Domain
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- Odell, Luke R. (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi,Univ Newcastle, Sch Environm & Life Sci, Chem, Callaghan, NSW 2308, Australia.;Uppsala Univ, Uppsala Biomed Ctr, Dept Med Chem, Organ Pharmaceut Chem, Box 574, SE-75123 Uppsala, Sweden.
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- Abdel-Hamid, Mohammed K. (author)
- Univ Newcastle, Sch Environm & Life Sci, Chem, Callaghan, NSW 2308, Australia.;Assiut Univ, Fac Pharm, Dept Med Chem, Assiut 71526, Egypt.
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- Hill, Timothy A. (author)
- Univ Newcastle, Sch Environm & Life Sci, Chem, Callaghan, NSW 2308, Australia.
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- Chau, Ngoc (author)
- The University of Sydney, 214 Hawkesbury Road, Westmead New South Wales , Australia
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- Young, Kelly A. (author)
- Univ Newcastle, Sch Environm & Life Sci, Chem, Callaghan, NSW 2308, Australia.
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- Deane, Fiona M. (author)
- Univ Newcastle, Sch Environm & Life Sci, Chem, Callaghan, NSW 2308, Australia.
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- Sakoff, Jennette A. (author)
- Calvary Mater Newcastle Hosp, Dept Med Oncol, Expt Therapeut Grp, Edith St, Waratah, NSW 2298, Australia.
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- Andersson, Sofia (author)
- Mälardalens högskola
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- Daniel, James A. (author)
- Univ Sydney, Childrens Med Res Inst, 214 Hawkesbury Rd, Westmead, NSW 2145, Australia.;Max Planck Inst Expt Med, Mol Neurobiol Grp, Hermann Rein Str 3, D-37075 Gottingen, Germany.
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- Robinson, Phillip J. (author)
- Univ Sydney, Childrens Med Res Inst, 214 Hawkesbury Rd, Westmead, NSW 2145, Australia.
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- McCluskey, Adam (author)
- Univ Newcastle, Sch Environm & Life Sci, Chem, Callaghan, NSW 2308, Australia.
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(creator_code:org_t)
- 2016-12-20
- 2017
- English.
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 60:1, s. 349-361
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- The large GTPase dynamin mediates membrane fission during clathrin-mediated endocytosis (CME). The aminopyrimidine compounds, were reported to disrupt clynamin localization to the plasina membrane via the PH domain and,iniplicate this mechanism in the inhibition of CME. We have used a computational approach of binding site identification, docking, and interaction energy calculations to design and synthesize a new library of aminopyrimidine analogues targeting site-2 of the pleckstrin homology (PH) domain. The optimized analogues showed low micromolar inhibition against both dynamin I (IC50 = 10.6 +/- 1.3 to 1.6 +/- 0.3 mu M) and CME (IC50(CME) = 65.9 +/- 7.7 to 17 +/- 1.1 mM), which makes this. series among The more potent inhibitors of dynamin.and CME yet reported. In:CME and growth inhibition cell-based assays, the data obtained Was consistent with dynamin inhibition. CEREP ExpresS profiling identified off-.target effects at the cholecystokinin, dopamine D-2, histamine H-1 and H-2, melanocortin, rnelatonin, muscarir* M-1 and M-3 neurokinin, opioid KOP and serotonin receptors.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
- NATURVETENSKAP -- Geovetenskap och miljövetenskap (hsv//swe)
- NATURAL SCIENCES -- Earth and Related Environmental Sciences (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Odell, Luke R.
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Abdel-Hamid, Moh ...
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Hill, Timothy A.
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Chau, Ngoc
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Young, Kelly A.
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Deane, Fiona M.
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show more...
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Sakoff, Jennette ...
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Andersson, Sofia
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Daniel, James A.
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Robinson, Philli ...
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McCluskey, Adam
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medicinal Chemis ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Earth and Relate ...
- Articles in the publication
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Journal of Medic ...
- By the university
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Uppsala University
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Mälardalen University