Sri International

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Large Scale Biology Corporation

Nahid S Waleh

Charles K Hiebert

Keith R Laderoute

Daniel Tuse

Paul H Johnson

Nurulain Zaveri

Jerome B Lazar

Cris M Olsen

Xiaoying Chen

Indira Sohel

Daniel Tus{acute Over (e)}

A Merrill Knapp

Compounds useful as chemotherapeutic, chemopreventive, and antiangiogenic agents are provided. The compounds are flavanoids, including flavanones, flavanols, and chalcones. The compounds have the structure of formula (I) wherein Rthrough Rand Rthrough Rare defined herein, and &#x3b1;, &#x3b2; and &#x3b3; are optional bonds, providing that when &#x3b1; is absent, &#x3b2; is present, and when &#x3b2; is absent, &#x3b1; is present. When &#x3b1; is present, preferred Rmoieties are selected from O, S, NH and CH, and when &#x3b1; is absent, preferred Rgroups are selected from OH, SH, NHand CH. When &#x3b3; is present, the preferred Rsubstituent is O, while when &#x3b3; is absent, the preferred Rsubstituent is OH. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

Flavanoids as chemotherapeutic, chemopreventive, and antiangiogenic agents

The present invention relates to methods for effectively inhibiting inflammatory diseases, such as Crohn's disease and ulcerative colitis. In other aspects, this invention relates to methods of reducing or inhibiting granulomas.

Method for inhibiting inflammatory disease

The present invention relates, inter alia, to compounds that bind tubulin and exhibit anti-mitotic properties and to methods of using such compounds to inhibit abnormal cell mitosis and, in particular, to inhibit tumor cell growth. In addition, methods are presented of treating mammalian diseases associated with undesired and uncontrolled angiogenesis.

Di-aryl ethers and their derivatives as anti-cancer agents

The present invention relates to methods for effectively inhibiting unwanted angiogenesis. More particularly, this invention relates to methods of treating diseases that show unwanted angiogenesis and to delivering anti-angiogenic activity to a mammal. In other aspects this invention relates to methods of reducing the level of tumor necrosis factor .alpha..

Methods for inhibiting angiogenesis

A method for obtaining heterologous peptides from fusion proteins wherein at least one of the fusion components is connective tissue-activating peptide-III is provided. Hirudin, a laminin B.sub.1 peptide and platelet factor 4 are polypeptides expressed using this method. DNA sequences encoding the fusion protein, vectors containing these sequences and transformed prokaryotic hosts useful in practicing the method of the present invention are also provided.

Method and vectors for stabilizing hirudin and human laminin B.sub.1

A synthetic structural gene encoding CTAP-III or CTAP-III-Leu21 including adaptors for the carboxy and amino terminal ends of the gene which contain start and stop codons and convenient restriction sites for use in cloning the gene is described. The gene was designed for efficient expression in bacteria and to include two unique restriction sites for BamHI and XbaI. Plasmid expression vectors that are derivatives of pBR322 that contain a ColE1 insert which includes the expression control sequence and structural gene for colicin are also described. Constructs for expressing CTAP-III, CTAP-III-Leu21, CTAP-III or CTAP-III-Leu21 having a nonpolar pentapeptide fused to its amino terminus, and fusion proteins of such CTAP-III proteins and a colicin fragment are prepared by inserting the synthetic structural gene into the vectors at positions in phase with the colicin expression control sequence and under the control thereof.

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Palo Alto, CA, United States of America

Nahid S Waleh