title: Studies on novel HIF activators, A-503451s.I. Producing organism, fermentation, isolation and structural elucidation.
abstract: In the course of our screening for activators of hypoxia-inducible factor (HIF), A-503451 A and virantmycin were isolated from the cultured broth of an actinomycete strain, Streptomyces sp. SANK 60101. From the same culture, the non-active homologs A-503451 B and D were also isolated. A-503451 A and virantmycin activated HIF-dependent reporter gene expression with EC50values of 8 and 17 ng ml-1, respectively. They are highly potent activators of HIF and thus may be therapeutically useful for erythropoiesis and neural cell protection.
authors.affiliation: Discovery Science and Technology Department, Daiichi Sankyo RD Novare Co., Ltd, Edogawa-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota-Takahata
authors.affiliation: Frontier Research Laboratories, Daiichi Sankyo Co. Ltd, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Discovery Science and Technology Department, Daiichi Sankyo RD Novare Co., Ltd, Edogawa-ku, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kizuka
authors.affiliation: Venture Science Laboratories, Daiichi Sankyo Co. Ltd, Shinagawa-ku, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ohyama
authors.affiliation: Biologics Pharmacology Research Laboratories, Daiichi Sankyo Co. Ltd, Shinagawa-ku, Tokyo, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kitamura-Miyazaki
authors.affiliation: Biologics Technology Research Laboratories, Daiichi Sankyo Co. Ltd, Oura-gun, Gunma, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Discovery Science and Technology Department, Daiichi Sankyo RD Novare Co., Ltd, Edogawa-ku, Tokyo, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Discovery Science and Technology Department, Daiichi Sankyo RD Novare Co., Ltd, Edogawa-ku, Tokyo, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd, Shinagawa-ku, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ando
mesh_terms: D005285:Fermentation; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000819:agonists*; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D011804:Quinolines; C030886:virantmycin