National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

USA As Represented by Secretary of the Navy

University of Illinois

The United States of America As Represented by the Secretary of

Other

Kirk R Gustafson

Michael R Boyd

James Brislin McMahon

Gordon M Cragg

John H Cardellina, Ii

Richard W Fuller

Robert H Shoemaker

Charles L Cantrell

Yoel Kashman

Curtis J Henrich

Lewis K Pannell

Heidi R Bokesch

Doel Soejarto

Laurent A Decosterd

Michael C Dean

Susan Elaine Bates

Robert W Robey

Suneet Shukla

Suresh V Ambudkar

Kentaro Takada

Laura K Cartner

Ian Parsons

Martin John Schnermann

William Douglas Figg

Paresma R Patel

Alan David Brooks

Thomas Joseph Sayers

Karen L Erickson

Nancy H Colburn

Ian Parson

John H Cardelina, Ii

Nancy Lynn Booth

Moon-II Kang

Matthew R Young

Susanna T S Chan

Embodiments of small molecule inhibitors of hypoxia inducible factor 1 (HIF-1) and pharmaceutical compositions thereof are disclosed. The disclosed compounds suppress HIF-1 activity by inhibiting the interaction between the HIF-1 &#x3b1; subunit and transcriptional co-activator protein p300. Embodiments of methods for making and using the small molecule inhibitors are also disclosed.

Hypoxia-inducible factor 1 (HIF-1) inhibitors

The present invention provides a compound of the formula (I) or (II), wherein Ris H, alkyl, alkenyl or aryl, Ris H, alkyl or aryl, Ris H, a alkyl, alkenyl or aryl, Rand R-Rare independently R, C(O)Ror SOR, wherein Ris H, alkyl, alkenyl or aryl, and Ris R, C(O)Ror SOR, wherein Ris H, alkyl, alkenyl or aryl. Rcan be unsubstituted or substituted with one or more oxo(&#x2550;O), OR, OC(O)R, OSOR, NHR, NHC(O)Rand NHSORgroups. Ris H, alkyl, alkenyl, or aryl. Rcan be unsubstituted or substituted with one or more groups such as oxo(&#x2550;O), OR, COR, CORand OC(O)R. Ris H, or a unsubstituted or substituted alkyl, alkenyl or aryl. The present invention further provides a composition comprising at least one compound of the present invention and a pharmaceutically acceptable carrier, alone or in combination with at least one additional active agent. The present invention further provides a method of treating a condition treatable by the inhibition of vacuolar-type (H+)-ATPase and a method of treating cancer. 

Biologically active macrolides, compositions, and uses thereof

Disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells, reducing resistance of a cancer cell to a chemotherapeutic agent, a method of inhibiting ABCG2, Pgp, or MRP1 in a mammal afflicted with cancer, and a method of increasing the bioavailability of an ABCG2 substrate drug in a mammal. The methods comprise administering effective amounts of certain compounds to the mammal, for example, a compound of the formula (I): wherein R, R, R, X, X, X, a, and b are as described herein. Uses of these compounds in the preparation of a medicament are also disclosed. Also disclosed are compounds of formula (II), pharmaceutical compositions comprising such compounds and uses thereof.

Method of inhibiting ABCG2 and other treatment methods

Disclosed is a method of enhancing the response of cancer cells in a mammal to treatment with a death receptor ligand, which method comprises contacting the cancer cells with a death receptor ligand in conjunction with an effective amount of a compound described herein, for example, a cucurbitacin (I) or a withanolide (II). Also disclosed is a method of inducing apoptosis in cancer cells in a mammal, comprising contacting the cancer cells with a compound described herein, for example, a cucurbitacin (I) or a withanolide (II) and also contacting the cancer cells with a death receptor ligand, whereby apoptosis is induced in the cancer cells. 

Method of sensitizing cancer cells to the cytotoxic effects of death receptor ligands in cancer treatment

The present invention provides a compound of the formula (I) or (II, wherein Ris H, alkyl, alkenyl or aryl, Ris H, alkyl or aryl, Ris H, a alkyl, alkenyl or aryl, Rand R-Rare independently R, C(O)Ror SOR, wherein Ris H, alkyl, alkenyl or aryl, and Ris R, C(O)Ror SOR, wherein Ris H, alkyl, alkenyl or aryl. Rcan be unsubstituted or substituted with one or more oxo(&#x2550;O), OR, OC(O)R, OSOR, NHR, NHC(O)Rand NHSORgroups. Ris H, alkyl, alkenyl, or aryl. Rcan be unsubstituted or substituted with one or more groups such as oxo(&#x2550;O), OR, COR, CORand OC(O)R. Ris H, or a unsubstituted or substituted alkyl, alkenyl or aryl. The present invention further provides a composition comprising at least one compound of the present invention and a pharmaceutically acceptable carrier, alone or in combination with at least one additional active agent. The present invention further provides a method of treating a condition treatable by the inhibition of vacuolar-type (H+)-ATPase and a method of treating cancer. 

An embodiment of the invention provides a pharmaceutical composition comprising a compound of formula (I) a pharmaceutically acceptable salt, prodrug, hydrate, or solvate thereof. Another embodiment of the invention provides a method of treating or preventing a condition associated with increased expression and/or activity of an NF&#x3ba;B pathway using same compounds. A further embodiment of the invention provides a method of diagnosing a condition in an individual using same compounds. 

Nuclear factor kappa B pathway inhibitor composition and use of same

A composition comprising a substantially purified compound of the formula: in combination with at least one additional therapeutic agent, and methods of preventing or treating cancer and a condition treatable by the inhibition of vacuolar-type (H+)-ATPase.

Chondropsin-class antitumor V-ATPase inhibitor compounds, compositions and methods of use thereof

Disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells, reducing resistance of a cancer cell to a chemotherapeutic agent, a method of inhibiting ABCG2, Pgp, or MRP1 in a mammal afflicted with cancer, and a method of increasing the bioavailability of an ABCG2 substrate drug in a mammal. The methods comprise administering effective amounts of certain compounds to the mammal, for example, a compound of the formula (I): Formula (I), wherein R, R, R, X, X, X, a, and b are as described herein. Uses of these compounds in the preparation of a medicament are also disclosed. Also disclosed are compounds of formula (II), pharmaceutical compositions comprising such compounds and uses thereof. 

Botryllamides and method of inhibiting PGP in a mammal afflicted with cancer

Chondropsin-class antitumor V-atpase inhibitor compounds, compositions and methods of use thereof

The present invention provides a compound of formula (II). The present invention further provides a composition comprising at least one compound of the present invention and a pharmaceutically acceptable carrier, alone or in combination with at least one additional active agent. The present invention further provides a method of treating a condition treatable by the inhibition of vacuolar-type (H+)-ATPase and a method of treating cancer.

A substantially purified compound of the formula: a composition comprising a therapeutically effective amount of at least one compound of the formula, alone or in combination with at least one additional therapeutic agent, and methods of preventing or treating cancer and a condition treatable by the inhibition of vacuolar-type (H+)-ATPase.

Chondropsin-class antitumor v-atpase inhibitor compounds, compositions and methods of use thereof

The present invention provides a compound of the formula (I). The present invention further provides a composition comprising at least one compound of the present invention and a pharmaceutically acceptable carrier, alone or in combination with at least one additional active agent. The present invention further provides a method of treating a condition treatable by the inhibition of vacuolar-type (H+)-ATPase and a method of treating cancer.

The present invention provides antiviral proteins (collectively referred to as cyanovirins), conjugates thereof, DNA sequences encoding such agents, host cells containing such DNA sequences, antibodies directed to such agents, compositions comprising such agents, and methods of obtaining and using such agents.

Antiviral proteins and peptides, DNA coding sequences therefor, and uses thereof

Growing community of inventors

Frederick, MD, United States of America

Kirk R Gustafson