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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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/139452
ISSN
2014 Impact Factor: 2.420
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

 

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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