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Iminochromene Inhib...
Iminochromene Inhibitors of Dynamins I and II GTPase Activity and Endocytosis
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Hill, Timothy A. (author)
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Mariana, Anna (author)
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Gordon, Christopher P. (author)
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- Odell, Luke R. (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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Robertson, Mark J. (author)
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McGeachie, Andrew B. (author)
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Chau, Ngoc (author)
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Daniel, James A. (author)
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Gorgani, Nick N. (author)
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Robinson, Phillip J. (author)
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McCluskey, Adam (author)
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(creator_code:org_t)
- American Chemical Society (ACS), 2010
- 2010
- English.
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 53:10, s. 4094-4102
- 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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- Herein we report the synthesis of discrete iminochromene (“iminodyn”) libraries (14−38) as potential inhibitors of dynamin GTPase. Thirteen iminodyns were active (IC50 values of 260 nM to 100 μM), with N,N-(ethane-1,2-diyl)bis(7,8-dihydroxy-2-iminochromene-3-carboxamide) (17), N,N-(ethane-1,2-diyl)bis(7,8-dihydroxy-2-iminochromene-3-carboxamide) (22), and N,N-(ethane-1,2-diyl)bis(7,8-dihydroxy-2-iminochromene-3-carboxamide) (23) (IC50 values of 330 ± 70, 450 ± 50, and 260 ± 80 nM, respectively) being the most potent. Five of the most potent iminodyns all inhibited dynamins I and II approximately equally. Iminodyn-22 displayed uncompetitive inhibition with respect to GTP. Selected iminodyns were evaluated for their ability to block receptor mediated endocytosis (RME, mediated by dynamin II) and synaptic vesicle endocytosis (SVE, mediated by dynamin I), with 17 showing no activity while 22 returned RME and SVE IC50 values of 10.7 ± 4.5 and 99.5 ± 1.7 μM, respectively. The iminodyns reported herein represent a new chemical class of the first nanomolar potent dynamin inhibitors that are also effective endocytosis inhibitors.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- PHARMACY
- FARMACI
- Organic Pharmaceutical Chemistry
- Organisk farmaceutisk kemi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hill, Timothy A.
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Mariana, Anna
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Gordon, Christop ...
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Odell, Luke R.
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Robertson, Mark ...
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McGeachie, Andre ...
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show more...
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Chau, Ngoc
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Daniel, James A.
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Gorgani, Nick N.
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Robinson, Philli ...
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McCluskey, Adam
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show less...
- 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 Pharmaceutical S ...
- Articles in the publication
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Journal of Medic ...
- By the university
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Uppsala University