title: Conformational significance of EH21A1-A4, phenolic derivatives of geldanamycin, for Hsp90 inhibitory activity.
abstract: Hsp90 is an attractive chemotherapeutic target because it is essential to maturation of multiple oncogenes. We describe the conformational significance of EH21A1-A4, phenolic derivatives of geldanamycin isolated from Streptomyces sp. Their native free structures are similar to the active form of geldanamycin bound to Hsp90 protein. Their conformational character is a probable reason for their high-affinity binding. Lack of toxic benzoquinone in EH21A1-A4 also adds to their potential as lead compounds for anti-tumor drugs.
authors.affiliation: BioFrontier Laboratories, Kyowa Hakko Kogyo Co., Ltd., 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Onodera
authors.forename: Masami
authors.initials: M
authors.lastname: Kaneko
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Uochi
authors.forename: Jun
authors.initials: J
authors.lastname: Funahashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakashima
authors.forename: Shiro
authors.initials: S
authors.lastname: Soga
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shunichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Endang S
authors.initials: ES
authors.lastname: Rahayu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanda
authors.forename: Michio
authors.initials: M
authors.lastname: Ichimura
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D016227:Benzoquinones; D045744:Cell Line, Tumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013302:Streptomyces / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C001277:geldanamycin