Tularik Limited

Amgen Inc.

M Catherine Amaral

Jin-Long Chen

Ning Zhang

Steven L McKnight

Bei Shan

R Marc Learned

Juan Carlos Jaen

Fabienne Charles De La Brousse

David Johnston

Fabienne C De La Brousse

Paul Rafferty

Compounds, compositions and methods are provided that are useful in the treatment or prevention of a condition or disorder mediated by an uncoupling protein. In particular, the compounds of the invention modulate the expression and/or activity of UCP3. The subject compositions are particularly useful in the treatment of obesity and type II diabetes, and associated diseases 

Bis-aryl thiazole derivatives

The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.

Cell-based drug screens for regulators of gene expression

The invention provides methods and compositions relating to a novel family of UCP3 polypeptides and related nucleic acids involved in metabolic regulation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed mUCP3 encoding nucleic acids or purified from mammalian cells. The invention provides isolated mUCP3 hybridization probes, knock-out/in constructs and primers capable of specifically hybridizing with the disclosed mUCP3 genes, mUCP3-specific binding agents such as specific antibodies, animals and cells modified with the subject mUCP3 nucleic acids, and methods of making and using the subject compositions in the biopharmaceutical industry.

UCP3 genes

Murine UCP3 polypeptides

The invention relates to regulators of UCP3 gene transcription, including novel UCP3 transcriptional promoters. UCP3 promoters are used in diagnosis and pharmaceutical development. In particular, transfected cells comprising UCP3 transcriptional regulators operably linked to a reporter are used in high-throughput pharmaceutical screens.

Assays for identifying agents which affect regulators of UCP3 gene

The invention relates to regulators of UCP2 gene transcription, including novel UCP2 transcriptional promoters. UCP2 gene promoters are used in diagnosis and pharmaceutical development. In particular, transfected cells comprising UCP2 gene promoters operably linked to a reporter are used in high-throughput pharmaceutical screens.

Method of identifying agents that modulate UCP2 promoter activity

The invention relates to regulators of UCP3 gene transcription, including novel UCP3 transcriptional promoters. UCP3 gene promoters are used in diagnosis and pharmaceutical development. In particular, transfected cells comprising UCP3 gene promoters operably linked to a reporter are used in high-throughput pharmaceutical screens.

Regulators of UCP3 gene expression

The invention provides methods and compositions relating to a novel family of genes, mUCP3s, involved in metabolic regulation. The polypeptides may be produced recombinantly from transformed host cells from the disclosed mUCP3 encoding nucleic acids or purified from mammalian cells. The invention provides isolated mUCP3 hybridization probes, knock-out/in constructs and primers capable of specifically hybridizing with the disclosed mUCP3 genes, mUCP3-specific binding agents such as specific antibodies, animals and cells modified with the subject mUCP3 nucleic acids, and methods of making and using the subject compositions in the biopharmaceutical industry.

Growing community of inventors

Roswell, GA, United States of America

M Catherine Amaral