title: A nonimmunosuppressive triene-modified rapamycin analog is a potent inhibitor of peptidyl prolyl cis-trans isomerase.
abstract: A triene-modified analog of the potent immunosuppressive agent rapamycin was found to be a potent inhibitor of the peptidyl prolyl cis-trans isomerase activity of human FKBP (Ki = 12.5 nM). This analog was not immunosuppressive in a thymocyte proliferation assay itself, but was able to antagonize the effect of rapamycin. This new analog should be useful as a mechanistic probe for macrocyclic immunosuppressants.
authors.affiliation: Wyeth-Ayerst Research, Princeton, NJ 08543.
authors.forename: T D
authors.initials: TD
authors.lastname: Ocain
authors.forename: D
authors.initials: D
authors.lastname: Longhi
authors.forename: R J
authors.initials: RJ
authors.lastname: Steffan
authors.forename: R G
authors.initials: RG
authors.lastname: Caccese
authors.forename: S N
authors.initials: SN
authors.lastname: Sehgal
mesh_terms: D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors*; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D003524:Cyclosporins / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D019696:Peptidylprolyl Isomerase; D010880:Piperidines / Q000494:pharmacology*; D011090:Polyenes / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
chemical_list: D002352:Carrier Proteins; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D010880:Piperidines; D011090:Polyenes; D011724:Pyridazines; D011994:Recombinant Proteins; C081453:WAY 124466; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus