title: A study of the correlation between cyclophilin binding and in vitro immunosuppressive activity of cyclosporine A and analogues.
abstract: In order to establish whether CyP is the pharmacologically relevant CsA receptor, the CyP binding v immunosuppressive activity was measured for an extensive, structurally varied group of CsA analogues. Overall, CyP binding was found to parallel immunosuppressive activity. Other than MeAla6-CsA, the few exceptions to the correlation could be ascribed to cellular metabolism. These results strongly implicate CyP or a related protein in the mechanism of action of cyclosporine.
authors.affiliation: Department of Medicinal Chemistry, Immunology and Inflammation, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
authors.forename: P L
authors.initials: PL
authors.lastname: Durette
authors.forename: J
authors.initials: J
authors.lastname: Boger
authors.forename: F
authors.initials: F
authors.lastname: Dumont
authors.forename: R
authors.initials: R
authors.lastname: Firestone
authors.forename: R A
authors.initials: RA
authors.lastname: Frankshun
authors.forename: S L
authors.initials: SL
authors.lastname: Koprak
authors.forename: C S
authors.initials: CS
authors.lastname: Lin
authors.forename: M R
authors.initials: MR
authors.lastname: Melino
authors.forename: A A
authors.initials: AA
authors.lastname: Pessolano
authors.forename: J
authors.initials: J
authors.lastname: Pisano
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003524:Cyclosporins / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D015759:Ionomycin; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D019696:Peptidylprolyl Isomerase; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D003524:Cyclosporins; D004987:Ethers; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015759:Ionomycin; D019696:Peptidylprolyl Isomerase; D013755:Tetradecanoylphorbol Acetate