Abstract: Compounds, compositions and methods are provided that are useful in the treatment of chemokine receptor-mediated conditions and diseases. In particular, the invention provides compounds which modulate CCR4 function or a CCR4-mediated response. The subject compounds and compositions are useful for the treatment or prevention of inflammatory conditions and diseases.
Type:
Application
Filed:
May 22, 2002
Publication date:
January 23, 2003
Applicant:
Tularik Inc.
Inventors:
Tassie Collins, Hossen Mahmud, Jonathan Houze, Alan Xi Huang, Julio C. Medina, Xuemei Wang, Feng Xu, Qingge Xu, Liusheng Zhu
Abstract: The present application provides methods of assaying for compounds that inhibit premature translation termination and nonsense mediated RNA decay in cells.
Type:
Application
Filed:
August 21, 2002
Publication date:
January 9, 2003
Applicant:
Tularik Inc.
Inventors:
Holger Beckmann, Marc Learned, Stuart Peltz, Kevin Czaplinski
Abstract: This invention provides methods and compositions that are useful for modulating cholesterol levels in a cell, and for identifying compounds that can tested for ability to modulate cholesterol levels in mammals. In vitro assays for prescreening to identify candidate therapeutic agents for modulation of cholesterol metabolism are provided. These methods involve analyzing the effect of a test compound on the binding of FXR to a ligand for FXR. Such ligands include, for example, bile acids, coactivators, and corepressors. The methods and compositions involve modulating FXR-mediated expression of genes involved in cholesterol metabolism.
Abstract: The present invention provides nucleic acid and protein sequences for a Th-1 cell-specific protein, Chandra. The herein-disclosed sequences can be used for any of a number of purposes, including for the specific detection of Th1 lymphocytes, for the identification of molecules that associate with and/or modulate the activity of Chandra, to diagnose any of a number of conditions associated with Th1 or Th2 cell activity, or to modulate the number and/or activity of Th1 or Th2 lymphocytes in a mammal.
Abstract: Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula I and an antineoplastic agent such as gemcitabine or paclitaxel.
Type:
Application
Filed:
November 2, 2001
Publication date:
November 28, 2002
Applicant:
Tularik Inc.
Inventors:
Susan Schwendner, Pieter Timmermans, Jacqueline Walling
Abstract: Compounds and compositions are provided that bind to the CCR4 chemokine receptor and which are useful for treating diseases associated with CCR4 activity, such as contact hypersensitivity.
Type:
Application
Filed:
October 11, 2001
Publication date:
November 21, 2002
Applicant:
Tularik Inc.
Inventors:
Tassie Collins, Daniel J. Dairaghi, Hossen Mahmud, Brian E. McMaster, Julio C. Medina, Thomas J. Schall, Feng Xu, Xuemei Wang
Abstract: The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, vascular restenosis, microbial infections, and psoriasis, or as lead compounds for the development of such agents.
Type:
Grant
Filed:
July 18, 1997
Date of Patent:
November 19, 2002
Assignee:
Tularik Inc.
Inventors:
John A. Flygare, Julio Cesar Medina, Bei Shan, David Louis Clark, Terry J. Rosen
Abstract: Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.
Type:
Application
Filed:
December 11, 2001
Publication date:
November 14, 2002
Applicant:
Tularik Inc.
Inventors:
Julio C. Medina, Michael G. Johnson, An-Rong Li, Jiwen Liu, Alan Xi Huang, Liusheng Zhu, Andrew P. Marcus
Abstract: The invention provides methods and compositions relating to an I&kgr;B kinase, IKK-&agr;, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKK-&agr; encoding nucleic acids or purified from human cells. The invention provides isolated IKK-&agr; hybridization probes and primers capable of specifically hybridizing with the disclosed IKK-&agr; genes, IKK-&agr;-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.
Type:
Grant
Filed:
July 2, 1998
Date of Patent:
November 12, 2002
Assignee:
Tularik Inc.
Inventors:
Mike Rothe, Zhaodan Cao, Catherine Régnier
Abstract: The present invention provides compositions and methods for treating proliferative disorders using combination therapies of lometrexol and other therapeutically active agents. The methods include administration of lometrexol with one or more therapeutically active agents where lometrexol and the therapeutically active agent(s) are delivered in a single composition, where they are administered in separate compositions in a simultaneous manner, where lometrexol is administered first, followed by the therapeutically active agent(s), as well as where the therapeutically active agent(s) is delivered first, followed by lometrexol. In preferred embodiments, the therapeutically active agent(s) has antiproliferative properties.
Type:
Application
Filed:
December 5, 2001
Publication date:
October 24, 2002
Applicant:
Tularik Inc.
Inventors:
Jacqueline Mary Walling, Heather Kay Webb, Alan Hilary Calvert, David R. Newell
Abstract: The present invention provides compounds, compositions and methods for the inhibition or treatment of conditions or disorders modulated by the STAT transcription factors, particularly STAT4 and STAT6. Additionally, the compounds are useful for the diagnosis of conditions dependent on STAT signaling.
Type:
Application
Filed:
November 7, 2001
Publication date:
October 17, 2002
Applicant:
Tularik Inc.
Inventors:
Alan Huang, Jiwen Liu, Julio Medina, Xuemei Wang, Feng Xu, Liusheng Zhu
Abstract: The present invention provides methods, reagents, and kits for diagnosing and treating cancer in a mammal, e.g., a human. This invention is based upon the discovery that Pellino 1 or 2 is overexpressed and/or amplified in cancer. Methods to detect cancer or a propensity to develop cancer, to monitor the efficacy of a cancer treatment, and to treat cancer, by inhibiting the expression and/or activity of Pellino 1 or 2 in a cancer cell are included.
Type:
Application
Filed:
December 28, 2001
Publication date:
October 17, 2002
Applicant:
Tularik Inc.
Inventors:
Scott Powers, David Mu, Phil Xiang, Yue Peng
Abstract: This invention provides methods and compositions that are useful for modulating cholesterol levels in a cell, and for identifying compounds that can tested for ability to modulate cholesterol levels in mammals. In vitro assays for prescreening to identify candidate therapeutic agents for modulation of cholesterol metabolism are provided. These methods involve analyzing the effect of a test compound on the binding of FXR to a ligand for FXR. Such ligands include, for example, bile acids, coactivators, and corepressors. The methods and compositions involve modulating FXR-mediated expression of genes involved in cholesterol metabolism.
Abstract: Compounds, compositions and methods are provided that are useful in the treatment and prevention of certain viral infections and associated diseases. In particular, the compounds of the invention inhibit the activity of a viral RNA polymerase. The subject methods are particularly useful in the treatment of diseases causes by hepatitis C virus infection.
Type:
Application
Filed:
April 5, 2001
Publication date:
October 3, 2002
Applicant:
Tularik Inc.
Inventors:
Jay P. Powers, Juan C. Jaen, Derek E. Piper, Nigel P.C. Walker, Yang Li
Abstract: The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents.
Type:
Application
Filed:
October 5, 2001
Publication date:
October 3, 2002
Applicant:
Tularik Inc.
Inventors:
John A Flygare, Julio Cesar Medina, Bei Shan, David Louis Clark, Terry J. Rosen
Abstract: The present application provides methods of assaying for compounds that inhibit premature translation termination and nonsense mediated RNA decay in cells.
Abstract: The present invention provides compounds, pharmaceutical compositions and methods that are useful in modulating the farnesoid X receptor (FXR). As FXR is involved in negatively controlling the expression level of cholesterol 7&agr;-hydroxylase (cyp7a), the rate-limiting enzyme involved in the oxidative metabolism of cholesterol into bile acids, the compounds described herein find utility in treating diseases associated with abnormally high or low cholesterol levels. In certain aspects, the FXR modulators (e.g., antagonists) described herein block the negative feed-back downregulation of cyp7a expression produced by certain cholic acids, the endogenous ligands for FXR. Moreover, as FXR forms heterodimers with the retinoid X receptor (RXR) in some cell types, modulation of the level of FXR activity in cells has a wide range of effects on a variety of biological processes which are mediated by RXR or other RXR-interacting proteins such as PPAR&ggr; and PPAR&agr;.
Type:
Application
Filed:
August 31, 2001
Publication date:
August 29, 2002
Applicant:
Tularik Inc.
Inventors:
Jonathan Houze, Sharon McKendry, Joshua P. Gergely, Yi Xia, Bei Shan, Frank Kayser
Abstract: The invention provides methods and compositions relating to Suppressor of Death Domain (SODD) proteins which regulate cellular signal transduction and transcriptional activation, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed SODD encoding nucleic acids or purified from human cells. The invention provides isolated SODD hybridization probes and primers capable of specifically hybridizing with the disclosed SODD genes, SODD-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.
Abstract: Derivatives of known tubulin-binding compounds are provided in which a (poly)fluorobenzene, a fluoropyridine, or a fluoronitrobenzene moiety is incorporated or added to the structure. These derivatives can be used as antimitotic agents and can be considered covalent modifiers of tubulin. The strategy developed for each of the compounds is to i) append a fluorinated electrophile (e.g., pentafluorophenylsulfonamido, 2-fluoropyridyl, or 3,5-dinitro-4-fluorophenyl) to an existing functional group in a natural product, ii) replace an aromatic ring in a natural product with a fluorinated electrophile, or iii) attach a fluorinated electrophile to an open valence in a portion of the molecule that will not interfere with recognition and binding to the tubulin site. Derivatives are provided based on colchicine, steganacin, podophyllotoxin, nocodazole, combretastatin, curacin A, vinblastine, vincristine, dolastatin, 2-methoxyestradiol, dihydroxy-pentamethoxyflavanone and others.
Type:
Grant
Filed:
December 15, 1999
Date of Patent:
August 13, 2002
Assignee:
Tularik Inc.
Inventors:
David Clark, Walter Frankmoelle, Jonathan Houze, Juan C. Jaen, Julio C. Medina
Abstract: The invention provides methods and compositions for screening for pharmacological agents which regulate satiety, fat metabolism and/or the type II diabetes mellitus in mammals, and in particular, agents active at regulating the level of ob gene expression. An exemplary assay involves (a) contacting a mammalian adipocyte comprising a mutant of a native ob allele encoding a reporter of ob gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native ob 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 ob gene expression.
Type:
Grant
Filed:
July 13, 1998
Date of Patent:
August 13, 2002
Assignee:
Tularik Inc
Inventors:
Fabienne Charles de la Brousse, Jin-long Chen