title: 3,5-Bis(trifluoromethyl)pyrazoles: a novel class of NFAT transcription factor regulator.
abstract: A series of bis(trifluoromethyl)pyrazoles (BTPs) has been found to be a novel inhibitor of cytokine production. Identified initially as inhibitors of IL-2 synthesis, the BTPs have been optimized in this regard and even inhibit IL-2 production with a 10-fold enhancement over cyclosporine in an ex vivo assay. Additionally, the BTPs show inhibition of IL-4, IL-5, IL-8, and eotaxin production. Unlike the IL-2 inhibitors, cyclosporine and FK506, the BTPs do not directly inhibit the dephosphorylation of NFAT by calcineurin.
authors.affiliation: Immunological Diseases Research, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, Illinois 60064-6217, USA. stevan.w.djuric@abbott.com
authors.forename: S W
authors.initials: SW
authors.lastname: Djuric
authors.forename: N Y
authors.initials: NY
authors.lastname: BaMaung
authors.forename: A
authors.initials: A
authors.lastname: Basha
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: J R
authors.initials: JR
authors.lastname: Luly
authors.forename: D J
authors.initials: DJ
authors.lastname: Madar
authors.forename: R J
authors.initials: RJ
authors.lastname: Sciotti
authors.forename: N P
authors.initials: NP
authors.lastname: Tu
authors.forename: F L
authors.initials: FL
authors.lastname: Wagenaar
authors.forename: P E
authors.initials: PE
authors.lastname: Wiedeman
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Ballaron
authors.forename: J
authors.initials: J
authors.lastname: Bauch
authors.forename: Y W
authors.initials: YW
authors.lastname: Chen
authors.forename: X G
authors.initials: XG
authors.lastname: Chiou
authors.forename: T
authors.initials: T
authors.lastname: Fey
authors.forename: D
authors.initials: D
authors.lastname: Gauvin
authors.forename: E
authors.initials: E
authors.lastname: Gubbins
authors.forename: G C
authors.initials: GC
authors.lastname: Hsieh
authors.forename: K C
authors.initials: KC
authors.lastname: Marsh
authors.forename: K W
authors.initials: KW
authors.lastname: Mollison
authors.forename: M
authors.initials: M
authors.lastname: Pong
authors.forename: T K
authors.initials: TK
authors.lastname: Shaughnessy
authors.forename: M P
authors.initials: MP
authors.lastname: Sheets
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Trevillyan
authors.forename: U
authors.initials: U
authors.lastname: Warrior
authors.forename: C D
authors.initials: CD
authors.lastname: Wegner
authors.forename: G W
authors.initials: GW
authors.lastname: Carter
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy; D002455:Cell Division; D054413:Chemokine CCL11; D019742:Chemokines, CC; D020650:Combinatorial Chemistry Techniques; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D000882:Haplorhini; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008156:Luciferases / Q000235:genetics; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C515456:CCL11 protein, human; C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015848:Interleukin-5; D016209:Interleukin-8; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D011720:Pyrazoles; D014157:Transcription Factors; D015847:Interleukin-4; D016572:Cyclosporine; D008156:Luciferases