AS1387392, a novel immunosuppressive cyclic tetrapeptide compound with inhibitory activity against mammalian histone deacetylase

• Published in: Journal of antibiotics Vol. 63; no. 11; pp. 633 - 636
• Main Authors: Sasamura, Satoshi, Sakamoto, Kazutoshi, Takagaki, Shoji, Yamada, Toshiko, Takase, Shigehiro, Mori, Hiroaki, Fujii, Takashi, Hino, Motohiro, Hashimoto, Michizane
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2010; Japan Antibiotics Research Assoc; Nature Publishing Group
• Subjects: 631/154/436/2388; 631/1647/2230; 631/326/193; 639/638/403/936; Acremonium - chemistry; Animals; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Biotechnology & Applied Microbiology; Cell Proliferation - drug effects; Female; Fermentation; Histone Deacetylase Inhibitors - isolation & purification; Histone Deacetylase Inhibitors - pharmacokinetics; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - drug effects; Histone Deacetylases - metabolism; Humans; Immunology; Immunosuppressive Agents - isolation & purification; Immunosuppressive Agents - pharmacology; Life Sciences; Life Sciences & Biomedicine; Male; Mammals; Medicinal Chemistry; Mice; Mice, Inbred BALB C; Microbiology; Organic Chemistry; original-article; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacokinetics; Peptides, Cyclic - pharmacology; Pharmacology & Pharmacy; Rats; Rats, Inbred Lew; Science & Technology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; AS1387392; FR235222; histone deacetylase inhibitor; fermentation; immunosuppressant; isolation; sp; Acremonium sp; FUNGAL METABOLITE; BIOLOGICAL-ACTIVITIES; AGENTS; TRANSPLANTATION; HDAC
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2010.51

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.