FR235222, a fungal metabolite, is a novel immunosuppressant that inhibits mammalian histone deacetylase (HDAC) II. Biological activities in animal models.
FR235222, a novel immunosuppressant which possesses potent inhibitory effects on the activity of mammalian histone deacetylases (HDACs), has been isolated from the fermentation broth of a fungus, Acremonium sp. No. 27082. FR235222 exhibited marked immunosuppressive effects on mouse ex vivo splenic T-lymphocyte proliferation, mouse delayed type hypersensitivity (DTH) response, rat adjuvant-induced arthritis (AA) and rat heterotopic cardiac transplantation. These results showed potential clinical use of this compound as a new type immunosuppressant in the fields of autoimmune diseases and organ transplantations.
Mori
Hiroaki
H
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. hiroaki_mori@po.fujisawa.co.jp
Abe
Fumie
F
Furukawa
Satoko
S
Furukawa
Shigetada
S
Sakai
Fumihiko
F
Hino
Motohiro
M
Fujii
Takashi
T
D000164:Acremonium / Q000378:metabolism*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D056572:Histone Deacetylase Inhibitors; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D004791:Enzyme Inhibitors; C474179:FR 235222; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic