Eisai R&d Management Co., Ltd.

Mercian Corporation

Eisai Company, Limited

Susumu Takeda

Takashi Nakashima

Toshio Tsuchida

Masashi Yoshida

Tomohiro Sameshima

Mitsuo Nagai

Yoshihiko Kotake

Jun Niijima

Satoshi Yamamoto

Naoto Kawamura

Takashi Sakai

Tomonari Yamada

Akifumi Okuda

Kiyoshi Okamoto

Kazuyuki Dobashi

Yoshiharu Mizui

Toshimitsu Uenaka

Takao Yamori

Masanori Fujita

Naoki Asai

Motoko Matsufuji

Keisuke Komeda

Kumiko Kishi

Masao Iwata

Koji Norihisa

Yoshio Fukuda

Hiroshi Ishihara

Regina Mikie Kanada

Kazuhiro Machida

Katsura Kaneko

Taira Kato

Yoshiaki Asahi

The present invention provides polypeptides that participate in the biosynthesis of the pladienolide macrolide compounds, DNA that encodes these polypeptides and variants of this DNA, transformants that maintain all or a portion of this DNA or variant thereof, and a method of producing the pladienolide macrolide compounds using these transformants. More particularly, it provides an isolated pure DNA that contains at least one region encoding a polypeptide that participates in pladienolide biosynthesis; polypeptide encoded by this DNA; a self-replicating or integrated-replicating recombinant plasmid carrying this DNA; a transformant maintaining this DNA; and a method of producing a pladienolide, characterized by culturing this transformant on culture medium and collecting pladienolide from this culture medium.

DNA coding for polypeptide participating in biosynthesis of pladienolide

The present invention provides a novel method of producing the 12-membered ring macrolide compound 11107D having an antitumor activity by biological transformation. Starting material which is the 12-membered ring macrolide compound 11107B represented by the formula (I) is incubated in the presence of a strain belonging to the genus, the genusor the family Micromonosporaceae (for example,sp. AB-1704 strain (FERM BP-8551)), each of which has the ability of transforming the 12-membered ring macrolide compound 11107B into a 11107D substance represented by the formula (II), or a preparation of its cultured myceha and oxygen, and then 11107D substance which is a target material is collected from the treating solution. 

Method of producing macrolide compound

The present invention provides a novel bioactive substance having an antitumor activity and a process for producing it, and a medical use thereof. Namely, it provides a 12-membered ring macrolide compound represented by the following formula obtained from the incubation solution ofsp. Mer. 11107 or a variant thereof, a pharmacologically acceptable salt thereof or a hydrate of them, and a process for producing it. 

Bioactive substance

The present invention provides a method for stabilizing a macrolide compound, and an efficient method for producing the compound. Specifically, it provides a method for stabilizing a macrolide compound, in which a 12-membered ring macrolide compound, such as a compound expressed by the formula (1) and a cyclodextrin are both present, and a method for producing a macrolide compound, in which a cyclodextrin is made to be present in a culture broth of actinomycetes having an ability of producing the macrolide compound.

Method for stabilizing macrolide compounds

Compounds represented by the following general formula (I), pharmacologically acceptable salts thereof or hydrates of the same: (I) wherein W represents and R, R, R, R, R, Rand Rare the same or different and each represents hydrogen, etc. Because of inhibiting angiogenesis and inhibiting the production of VEGF particularly in hypoxia, the compounds (I) are useful as remedies for solid cancer.

Physiologically active substances

The present invention provides a novel bioactive substance having an antitumor activity and a process for producing it, and a medical use thereof. Namely, it provides a 12-membered ring macrolide compound represented by the following formula obtained from the incubation solution ofsp. Mer. 11107 or a variant thereof, a pharmacologically acceptable salt thereof or a hydrate of them, and a process for producing it

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Shizuoka, Japan

Susumu Takeda