AS1387392, a novel immunosuppressive cyclic tetrapeptide compound with inhibitory activity against mammalian histone deacetylase.
The novel immunosuppressant AS1387392 has been isolated from Acremonium sp. No. 27082. This compound showed a strong inhibitory effect against mammalian histone deacetylase and T-cell proliferation. Further, AS1387392 showed a good oral absorption, and its plasma concentration was higher than that of FR235222, an analog of AS1387392 that inhibited histone deacetylase previously reported. Given these findings, AS1387392 may represent an important new lead in developing immunosuppressant.
Sasamura
Satoshi
S
Pharmacology Research Laboratories, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan. satoshi.sasamura@jp.astellas.com
Sakamoto
Kazutoshi
K
Takagaki
Shoji
S
Yamada
Toshiko
T
Takase
Shigehiro
S
Mori
Hiroaki
H
Fujii
Takashi
T
Hino
Motohiro
M
Hashimoto
Michizane
M
D000164:Acremonium / Q000737:chemistry*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005285:Fermentation; D056572:Histone Deacetylase Inhibitors / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
C554554:AS 1387392; C474179:FR 235222; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic; D006655:Histone Deacetylases