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Article: New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein

TitleNew aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein
Authors
Keywordsa-FABP inhibitor
Aromatic substituted pyrazoles
Inflammation related diseases
Inflammatory response
Issue Date2011
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmcl
Citation
Bioorganic And Medicinal Chemistry Letters, 2011, v. 21 n. 10, p. 2949-2952 How to Cite?
Abstract
a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K i value below 1.0 nM, while did not inhibit h-FABP at 50 μM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. © 2011 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/139452
ISSN
2013 Impact Factor: 2.331
ISI Accession Number ID
Funding AgencyGrant Number
National Basic Research Program of China2010CB529706
2010CB9455000
2009CB940904
Chinese Academy of Sciences
National Natural Science Foundation30811120429
3097063
90813033
Funding Information:

We thank National Basic Research Program of China (Grant #2010CB529706, 2010CB9455000 and 2009CB940904), the 100-talent program of Chinese Academy of Sciences, and National Natural Science Foundation (Grant #30811120429, 3097063 and 90813033) for their financial support.

References

 

Author Affiliations
  1. The University of Hong Kong
  2. Chinese Academy of Sciences
  3. East China University of Science and Technology
DC FieldValueLanguage
dc.contributor.authorLiu, Xen_HK
dc.contributor.authorHuang, Xen_HK
dc.contributor.authorLin, Wen_HK
dc.contributor.authorWang, Den_HK
dc.contributor.authorDiao, Yen_HK
dc.contributor.authorLi, Hen_HK
dc.contributor.authorHui, Xen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorWu, Den_HK
dc.contributor.authorKe, Den_HK
dc.date.accessioned2011-09-23T05:50:09Z-
dc.date.available2011-09-23T05:50:09Z-
dc.date.issued2011en_HK
dc.identifier.citationBioorganic And Medicinal Chemistry Letters, 2011, v. 21 n. 10, p. 2949-2952en_HK
dc.identifier.issn0960-894Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/139452-
dc.description.abstracta-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K i value below 1.0 nM, while did not inhibit h-FABP at 50 μM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. © 2011 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_US
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmclen_HK
dc.relation.ispartofBioorganic and Medicinal Chemistry Lettersen_HK
dc.subjecta-FABP inhibitoren_HK
dc.subjectAromatic substituted pyrazolesen_HK
dc.subjectInflammation related diseasesen_HK
dc.subjectInflammatory responseen_HK
dc.subject.meshAdipocytes - drug effects-
dc.subject.meshAnti-Inflammatory Agents - chemical synthesis - chemistry - pharmacology-
dc.subject.meshDrug Design-
dc.subject.meshFatty Acid-Binding Proteins - antagonists and inhibitors-
dc.subject.meshPyrazoles - chemical synthesis - chemistry - pharmacology-
dc.titleNew aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding proteinen_HK
dc.typeArticleen_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bmcl.2011.03.063en_HK
dc.identifier.pmid21481589en_HK
dc.identifier.scopuseid_2-s2.0-79955561585en_HK
dc.identifier.hkuros194038en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955561585&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue10en_HK
dc.identifier.spage2949en_HK
dc.identifier.epage2952en_HK
dc.identifier.eissn1464-3405-
dc.identifier.isiWOS:000290024200033-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLiu, X=49861829500en_HK
dc.identifier.scopusauthoridHuang, X=9940392000en_HK
dc.identifier.scopusauthoridLin, W=36717896600en_HK
dc.identifier.scopusauthoridWang, D=14051219700en_HK
dc.identifier.scopusauthoridDiao, Y=36617062800en_HK
dc.identifier.scopusauthoridLi, H=36064230500en_HK
dc.identifier.scopusauthoridHui, X=26666795900en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridWu, D=7404297751en_HK
dc.identifier.scopusauthoridKe, D=35332543000en_HK

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