Burnham Institute for Medical Research

Other

The Texas A&M University System

Sanford-burnham Medical Research Institute

The Burnham Institute

Accumetrics, Inc.

Jeffrey W Smith

Steven J Kridel

Daniel Romo

Fumiko Axelrod

Gil Ma

Vikram C Purohit

Emily I Chen

Dennis A Durbin

Robert S Hillman

Debra M Meyer

Christopher P Carron

George A Nickols

Robyn Richardson

Dana D Hu

Boris I Ratnikov

Sung Wook Cho

Theodore T Lee

Changming Fang

Dwayne Hoffman

Manuel Zancanella

We have identified a new variant of ileal bile acid binding protein (IBABP), designated IBABP-L, which is a biomarker for colorectal cancer. The transcript for IBABP-L arises from an alternative start site and includes three exons that are absent in IBABP. IBABP-L also shares part of a fourth exon with IBABP. The protein encoded by IBABP-L contains a deduced 49 residue N-terminal sequence that is not found in the IBABP protein. The present invention provides methods for diagnosing colorectal cancer and other compositions and methods based on this discovery.

Compositions and methods for detection of colorectal cancer

The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and Rcomprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.

Beta-lactone compounds

The present invention features methods of treating a cancer in a subject by administering an effective amount of a beta-lactone to the subject. The invention also features methods of inhibiting angiogenesis in a subject by administering an effective amount of an inhibitor of fatty acid synthase to the subject. These methods can be used to treat a variety of cancers and other diseases and conditions. The invention also features methods of identifying beta-lactones and other compounds that can be used in the methods of the invention for the treatment of tumors, inhibition of angiogenesis, and the treatment of diseases and conditions that involve pathological angiogenesis. The invention also features methods of synthesizing beta-lactones and features novel beta-lactone compounds.

Method for the asymmetric synthesis of beta-lactone compounds

Derivatives of belactosin and their synthesis are disclosed. In certain embodiments, compounds of the present invention exhibit anti-cancer, antiviral, antibiotic, and/or auto-immune therapeutic abilities. In general, methods of synthesis disclosed herein allow for introduction of a variety of substituents at numerous positions as well as the facile introduction of a beta-lactone ring moiety. The synthetic steps comprise, in preferred embodiments, a tandem Mukaiyama aldol lactonization reaction. Data demonstrating the utility of some of the derivatives as proteasome inhibitors is also disclosed.

Belactosin derivatives as therapeutic agents/biological probes and their synthesis

The invention provides isolated MMP-2, MMP-9 and MT1-MMP selective substrate polypeptides or functional peptidomimetics. The selective substrate polypeptides contain the following sequences: MMP-2 selective substrate polypeptides contain SEQ ID NOS:1-27, MMP-9 selective substrate polypeptides contain SEQ ID NOS:28-35, and MT1-MMP selective substrate polypeptide contain SEQ ID NOS:36-40. In addition, the invention provides a method of preferentially directing a moiety to a site of MMP-2 activity by administering to a subject an effective amount of an isolated MMP-2 selective substrate polypeptide containing SEQ ID NOS:45-47 linked to a moiety. Also provided is a method of preferentially directing a moiety to a site of MMP-9 activity by administering to a subject an effective amount of an isolated MMP-9 selective substrate polypeptide containing SEQ ID NO:44 linked to a moiety, and preferentially directing a moiety to a site of MT1-MMP activity by administering to a subject an effective amount of an isolated MT1-MMP selective substrate polypeptide containing SEQ ID NOS:36-40 linked to a moiety.

Selective substrates for matrix metalloproteinases

The present invention features methods of treating a cancer in a subject by administering an effective amount of a beta-lactone to the subject. The invention also features methods of inhibiting angiogenesis in a subject by administering an effective amount of an inhibitor of fatty acid synthase to the subject. These methods can be used to treat a variety of cancers and other diseases and conditions. The invention also features methods of identifying beta-lactones and other compounds that can be used in the methods of the invention for the treatment of tumors, inhibition of angiogenesis, and the treatment of diseases and conditions that involve pathological angiogenesis.

Inhibition of fatty acid synthase by beta-lactones and other compounds for inhibition of cellular proliferation

A portable multi-purpose workstation assembly for allowing users to mount two engines side-by-side and to easily transfer parts from one engine to the other engine. The portable multi-purpose workstation assembly includes a base assembly including a plurality of elongate base members, and also including base connecting members interconnecting and supporting the elongate base members, and further including wheel assemblies upon which the elongate base members and the base connecting members are supported; and also includes a support assembly being adjustably mounted upon the base assembly, and including sleeve members being disposed about one of the elongate base members, and also including post members being attached to the sleeve members, and further including bracket assemblies being mounted upon the post members.

Portable multi-purpose workstation assembly

Monoclonal antibodies that recognize the &agr;,&bgr;,integrin receptor complex, but do not significantly bind to &agr;,&bgr;,, can be used in methods for treating &agr;,&bgr;,integrin-mediated diseases, such as tunor metastasis.

Methods for using anti-&agr;v&bgr;3 integrin antibody

The invention provides a method of disaggregating a ligand:integrin receptor complex. Specifically, the invention provides a method of disaggregating an existing platelet thrombus in a blood vessel in a subject, comprising administering to the subject a compound which dissociates fibrinogen bound to a first site on platelet glycoprotein IIB-IIIa, by binding a second interacting site on the platelet glycoprotein IIB-IIIa, thereby disaggregating the platelet thrombus. The present invention also provides a method of screening compounds for the ability to dissociate a ligand from its integrin receptor by binding an interacting second site, comprising contacting the compound with an existing ligand:integrin receptor complex and determining if the complex dissociates.

Integrin ligand dissociators

Methodology which avoids the problems associated with interference from whole blood is provided for instrumented determination of platelet binding function. Particularly, small particles to which fibrinogen is bound, and which contain an infrared light absorbing dye, are used to determine the binding of platelets in a whole blood sample to the fibrinogen. Agglutination of the platelets with the coated particles is determined by a change in infrared light absorption characteristics.

Growing community of inventors

San Diego, CA, United States of America

Jeffrey W Smith