The Burnham Institute

Sanford-Burnham Medical Research Institute

Burnham Institute for Medical Research

La Jolla Cancer Research Foundation

University of Pennsylvania

Torrey Pines Institute for Molecular Studies

University of California

The University of New Mexico

Burham Institute for Medical Research

John C Reed

Adam Godzik

Takaaki Sato

Shinichi Takayama

Quinn L Deveraux

Bin Guo

Shu-ichi Matsuzawa

Krzysztof Pawlowski

Maurizio Pellecchia

Ryosuke Takahashi

Xiao-kun Zhang

Siva Kumar Kolluri

Guy S Salvesen

Bingzhen Lin

Natalie Roy

Masayoshi Harigai

Bruce D Hammock

Ning Ke

Qihong Huang

Christian Stehlik

Sug Hyung Lee

Hiroko Maeda, Legal Representative

Qunli Xu

Toshiyuki Miyashita

Motoi Hanada

Richard Allen Houghten

John M Ostresh

Clemencia Pinilla

Adel Nefzi

Susumu Maeda

Ingo Tamm

Frederick F Pio

Jason S Damiano

Vasco A Oliveira

Hideki Hayashi

Kate Welsh

Loredana Fiorentino

Juan M Zapata

Larry A Sklar

Dayong Zhai

Zhi-Liang Chu

Eric R Prossnitz

Angela Wandinger-Ness

Peter C Simons

Kryzysztof Pawlowski

Kazuya Okada

Maryla Krajewska

Wilfried Roth

Frank Stenner-Liewen

Maria Eugenia Ariza

Aaron D Schimmer

Matsuzawa Shu-ichi

Mathewos Z Tessema

Stan Krajewski

Methods of using apogossypol and its derivatives for treating inflammation is disclosed. Also, there is described a group of compounds having structure A, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof are provided: wherein each R is independently selected from the group consisting of H, C(O)X, C(O)NHX, NH(CO)X, SONHX, and NHSOX, wherein X is selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, an alkylaryl, and a heterocycle. Compounds of group A may be used for treating various diseases or disorders, such as cancer.

Naphthalene-based inhibitors of anti-apoptotic proteins

The present invention provides a method for treating cancer in a mammal comprising contacting the cancer cells with a compound which is a apogossypol, derivative.

Methods and compounds useful to induce apoptosis in cancer cells

Compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and Bcl-Xare identified. These compounds have the ability to convert the activity of Bcl-2-family member proteins from anti-apoptotic to pro-apoptotic. Methods for inducing apoptosis are described, together with methods for identifying molecules that induce apoptosis through interaction with Bcl-2-family members.

Conversion of apoptotic proteins

A novel human member of the Bcl-2 family Bcl-B has been identified, which is closest in amino-acid sequence homology to the Boo (Diva) protein. The Bcl-B protein is widely expressed in adult human tissues. The Bcl-B protein modulates apoptosis. Bcl-B also binds Bcl-2, BCl-XL, and Bax but not Bak. Bcl-B displays a unique pattern of selectivity for binding and regulating the function of other members of the Bcl-2 family.

Apoptosis modulator Bcl-B and methods for making and using same

The invention provides polypeptides comprising inhibitor of apoptosis protein (IAP) family members, such as BmIAP initially derived fromBmN cells, and nucleic acids encoding them, and methods for making and using these compositions, including their use for inhibiting apoptosis.

Inhibitor of apoptosis proteins and nucleic acids and methods for making and using them

Provided herein are compositions and methods of detecting Bcl-B expression in cancer cells to prognose, monitor, or select therapies for cancers such as breast cancer, prostate cancer, lung cancer, or gastric cancer.

Detecting Bcl-B expression in cancer and uses thereof

The present invention relates to an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases, for example, an interaction of the X chromosome linked IAP (XIAP) and caspase-3, caspase-7 or caspase-9, wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a caspase such as caspase-3 or caspase-7. The invention also provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a pro-caspase such as pro-caspase-9. In addition, the invention also provides methods for identifying agents that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP. The invention further provides methods of reducing the severity of a pathologic condition in an individual by administering to the individual an agent that alters the caspase inhibitory activity of an IAP. In addition, the invention provides methods of modulating the ability of a population of cells to survive ex vivo by contacting the cells with an agent that alters the caspase inhibitory activity of an IAP in the cells.

Screening assays for agents that alter inhibitor of apoptosis (IAP) protein regulation of caspase activity

The invention provides Bcl-G polypeptides and encoding nucleic acids. Bcl-G polypeptides include Bcl-Gand Bcl-G. The invention also provides mouse Bcl-G. The invention also provides vectors containing Bcl-G nucleic acids, host cells containing such vectors, Bcl-G anti-sense nucleic acids and related compositions. The invention additionally provides Bcl-G oligonucleotides that can be used to hybridize to or amplify a Bcl-G nucleic acid. Anti-Bcl-G specific antibodies are also provided. Further provided are kits containing Bcl-G nucleic acids or Bcl-G specific antibodies. Such kits and reagents can be used to diagnose cancer, monitor response to therapy, or predict the prognosis of a cancer patient. The invention additionally provides methods of modulating apoptosis using Bcl-G polypeptides, encoding nucleic acids, or compounds that modulate the activity or expression of Bcl-G polypeptides. The methods for modulating apoptosis can be used to treat diseases such as cancer.

Bcl-G polypeptides, encoding nucleic acids and methods of use

Methods of identifying death receptor sensitizing compounds and methods of using death receptor sensitizing compounds are provided.

Death receptor sensitizing compounds and methods of use therefor

The present invention provides NB-ARC and CARD-containing proteins (NACs), nucleic acid molecules encoding NACs and antibodies specific for at least one NAC. The invention further provides chimeric NAC proteins. The invention also provides screening assays for identifying an agent that can effectively alter the association of a NAC with a NAC-associated protein. The invention further provides methods of modulating apoptosis in a cell by introducing into the cell a nucleic acid molecule encoding a NAC or an antisense nucleotide sequence. The invention also provides a method of using a reagent that can specifically bind to a NAC to diagnose a pathology that is characterized by an increased or decreased level of apoptosis in a cell.

Card proteins involved in cell death regulation

The present invention provides a family of BAG-1 related proteins from humans (BAG-1L, BAG-1, BAG-2, BAG-3, BAG-4 and BAG-5), the invertebrate(BAG-1, BAG-2) and the fission yeast(BAG-1A, BAG-1B) and the nucleic acid molecules that encode them.

Bag proteins and nucleic acid molecules encoding them

In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPS) and/or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and/or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and/or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and/or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein. Also provided are compositions and methods for targeting the destruction of selected polypeptides in eukaryotic cells based on the ubiquitin-independent mechanism by which ornithine decarboxylase is degraded by the 26S proteasome.

Nucleic acid encoding proteins involved in protein degradation, products and methods related thereto

In accordance with the present invention, there are provided methods for determining a prognosis of disease free or overall survival in a patient suffering from cancer. Also provided are methods for predicting the risk of tumor recurrence or spread in an individual having a cancer tumor. Methods for screening a cancer patient to determine the risk of tumor metastasis; methods for determining the proper course of treatment for a patient suffering from cancer; and kits for use in practising the invention methods.

Method for determining the prognosis of cancer patients by measuring levels of bag expression

The invention provides a method of identifying an effective compound that modulates the binding of Humanin to Bax or Bid. The invention also provides a method of identifying an effective compound that modulates an activity of Bax or Bid. In addition, the invention provides a method of identifying a Humanin-like compound that binds to Bax or Bid or modulates an activity of Bax or Bid, or inhibits the apoptotic activity of Bax or Bid. The invention further provides an isolated polypeptide containing a mitochondrial-derived form of Humanin (SEQ ID NO:3) or a functional fragment thereof where the fragment contains the methionine at position 16 of SEQ ID NO:3.

Methods for identifying modulators of apoptosis

In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPs) and/or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and/or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and/or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and/or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein.

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Rancho Santa Fe, CA, United States of America

John C Reed