Conformational significance of EH21A1-A4, phenolic derivatives of geldanamycin, for Hsp90 inhibitory activity.
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.
Onodera
Hideyuki
H
BioFrontier Laboratories, Kyowa Hakko Kogyo Co., Ltd., 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
Kaneko
Masami
M
Takahashi
Yuichi
Y
Uochi
Yumiko
Y
Funahashi
Jun
J
Nakashima
Takayuki
T
Soga
Shiro
S
Suzuki
Makoto
M
Ikeda
Shunichi
S
Yamashita
Yoshinori
Y
Rahayu
Endang S
ES
Kanda
Yutaka
Y
Ichimura
Michio
M
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
D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C001277:geldanamycin