Children's Medical Center Corporation

Takeda Chemical Industries, Inc.

Harvard College

Other

University of Pennsylvania

Children's Hospital Medical Center

Moses J Folkman

Robert J D'Amato

Robert Samuel Langer

Yuen Shing

Donald Elliot Ingber

Koichi Kato

Takeshi Fujita

Koichi Igarashi

Stephanie Taylor

Joseph Feder

Paul B Weisz

Shoji Kishimoto

William R Tolbert

Elias James Corey

Tsuneo Kanamaru

Mau-Jung Kuo

Robert W Thompson

Robert L Hannan

Harold Brem

Neil T Chen

The application discloses methods of treating mammalian diseases characterized by abnormal cell mitosis by administering estradiol derivatives including those comprising colchicine or combretastatin A-4 structural motifs of the general formulae found below in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the methods.

Estrogenic compounds as anti-mitotic agents

The present invention provides for the use of fumagillin or an O-substituted fumagillol derivative in conjunction with interferon which increases the angiogenic inhibitory action as compared with the agents administered alone. It has also been discovered that in the treatment of certain angiogenesis-induced diseases, the combination of the present invention is synergistic in angiogenesis inhibitory effect. The invention further provides a method for treatment of angiogenesis-induced diseases.

Methods of treating angiogenesis-induced diseases and pharmaceutical

This invention relates to methods of using O-substituted fumagillol derivatives or salts thereof preferably, O-(N-chloroacetylcarbamoyl) fumagillol, O-(N-chloroacetylcarbamoyl)dihydrofumagillol or O-(N-chloracetylcarbamoyl)-6'b-hydroxyfumagillol, which have angiogenesis inhibitory activity, in the treatment and prevention of various diseases caused or advanced by abnormally hyperactive angiogenesis, especially various inflammatory diseases (rheumatism, psoriasis, etc.), diabetic retinopathy and cancer and other angiogenesis-dependent tumors, especially Kaposi's sarcoma, breast cancer, colon cancer.

Method of treating tumors using O-substituted fumagillol derivatives

A recombinant non-glycosylated mammalian growth factor (BTC-GF) stimulates proliferation of human smooth muscle cells. Especially, the amino acid sequence of the protein deduced from the nucleotide sequence coding for human BTC-GF is as that comprising the amino acids No. 1 to No. 147 of FIG. 10 (SEQ ID NO:18) or the amino acids No. 1 to 80 of FIG. 10, (SEQ ID NO:18) and the amino acid sequence of the protein deduced from the nucleotide sequence coding for mouse BTC-GF is as that comprising the amino acids No. 1 to No. 146 of FIG. 9 (SEQ ID NO:17).

Smooth muscle mitogen and isolated DNA coding therefor

A recombinant non-glycosylated mammalian growth factor (BTC-GF) stimulates proliferation of human smooth muscle cells. Especially, the amino acid sequence of the protein deduced from the nucleotide sequence coding for human BTC-GF is as that comprising the amino acids No. 1 to No. 147 of FIG. 10 (SEQ ID NO:5) or the amino acids No. 1 to 80 of FIG. 10 (SEQ ID NO:18), and the amino acid sequence of the protein deduced from the nucleotide sequence coding for mouse BTC-GF is as that comprising the amino acids No. 1 to No. 146 of FIG. 9 (SEQ ID NO:17).

Smooth muscle mitogen peptides and DNA coding therefor

O-substituted fumagillol derivatives and its salts have an angiogenesis inhibiting activity and are useful for prophylaxis and treatment of diseases induced by abnormally stimulated neovascularization.

Angiogenesis inhibitory agent

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Brookline, MA, United States of America

Moses J Folkman