title: FR182876, a new microtubule modulator with high water-solubility, from a Streptomyces.
abstract: In the course of seeking new anti-tumor drugs, a new microtubule modulator with high water-solubility, FR182876, was isolated from a Streptomyces which also produces FR182877. Even modern spectroscopic methods could not solve the structure of FR182876 due to its structural complexity and chemical instability. Thus, we have combined chemical correlations with spectroscopic methods and determined its structure, which features a highly fused ring system and 3-methylhistidine. The latter is believed to contribute to both solubility in water and activity in promoting tubulin polymerization. FR182876 showed potent cytotoxicity against a panel of cancer cells at concentrations of 28-75 ng/ml.
authors.affiliation: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3, Tokodai, Tsukuba 300-2698, Japan. seiji_yoshimura@po.fujisawa.co.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Bunji
authors.initials: B
authors.lastname: Sato
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Takase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terano
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D012995:Solubility; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; C492084:FR 182876; D006576:Heterocyclic Compounds, 4 or More Rings