Abstract: The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating EGFR activity, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated EGFR activity.

Abstract: The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating EGFR activity, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated EGFR activity.

Abstract: The invention provides novel pyrimidine and pyridine derivatives and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine and pyridine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof.

Abstract: The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of Cannabinoid Receptor 1 (CB1).

Abstract: The invention provides substrate specificity profiles for flaviviral proteases (e.g., dengue proteases or West Nile protease). Optimal flaviviral protease substrate sequences, both to the prime side and non-prime side of the flaviviral protease recognition site, are disclosed herein. The flaviviral protease substrate sequences are used in designing substrates, inhibitors, and prodrugs. Flaviviral protease inhibitors based on substrate specificity are also provided.

Abstract: This invention relates to the discovery that the transcription factors Pbx1 and HMG1 are involved in retrovirus, e.g., HIV, replication. Thus, the invention provides methods of identifying modulators of these proteins. Such modulators can be used as reagents in in vitro assays to modulate expression of retroviral sequences and may be used to inhibit HIV replication in vivo.

Abstract: This invention provides methods of screening for compounds that inhibit herpesviral transcription and replication. The methods comprise screening test compounds for ability to enhance the activity of homeodomain transcription factor SATB1 or CDP in repressing transcription of herpesviral genes (e.g., the IE gene of cytomegalovirus). Transcriptional repression by SATB1 or CDP can be monitored using an expression vector comprising a reporter gene operably linked to an SATB1/CDP-binding transcription regulatory sequence of the herpesvirus. The invention further provides methods and pharmaceutical compositions for stimulating SATB1 or CDP-mediated transcriptional repression in a subject and for treating diseases and conditions associated with herpesviral infection.

Abstract: The invention provides general methods for preparing 2,9-, 2,6,9-, O6-aryl- and O6-alkyl-substituted purines in a combinatorial and traceless fashion. The methods involve, in some embodiments, Mitsunobu alkylation of 2-fluoro-6-phenylsulfenylpurine at N9 with alcohols in solution, followed by C2-capture of the purine core with a resin-bound amine and subsequent oxidation and displacement of the C6 sulfonyl group with amines and anilines.

Abstract: Anti-DR4 or Anti-DR5 antibody agonists, combined with apoptosis-inducing agents, synergistically induce apoptosis in cancer cells.

Abstract: This invention provides methods of screening for compounds that inhibit herpesviral transcription and replication. The methods comprise screening test compounds for ability to enhance the activity of homeodomain transcription factor PDX1 in repressing transcription of herpesviral genes (e.g., the IE gene of cytomegalovirus). Transcriptional repression by PDX1 can be monitored using an expression vector comprising a reporter gene operably linked to a PDX1-binding, upstream transcription regulatory sequence of the herpesvirus. The invention further provides methods and pharmaceutical compositions for stimulating PDX1-mediated transcriptional repression in a subject and for treating diseases and conditions associated with herpesviral infection.

Abstract: This invention provides novel NF-AT-modulatory polypeptides. The invention also provides methods for screening modulators of NF-AT. The methods comprise first screening test agents for modulators of an NF-AT-modulatory polypeptide and then further screening the identified modulating agents for modulators of NF-AT. The invention further provides methods and pharmaceutical compositions for modulating NF-AT bioactivities in a cell and for treating diseases and conditions mediated by abnormal NF-AT activities.

Abstract: This invention provides novel Epo-modulating polypeptides. The invention also provides methods for screening modulators of Epo expression. The methods comprise first screening test agents for modulators of an Epo-modulating polypeptide and then further screening the identified modulating agents for modulators of Epo expression. The invention further provides methods and pharmaceutical compositions for modulating Epo expression in cells and for treating diseases and conditions due to Epo deficiency.

Abstract: The present invention relates to immunosuppressant, process for their production, their uses and pharmaceutical compositions containing them. The invention provides a novel class of compounds useful in the treatment or prevention of diseases or disorders mediated by lymphocyte interactions, particularly diseases associated with EDG receptor mediated signal transduction.

Abstract: The present invention is based on a novel cell tagging approach called “Differential Tag Length” method (DTLA) that allows the quantitative analysis of a mixture of multiple cell types (e.g., strains) grown in very small cultivation volumes. DTLA can also be fully automated and adapted for a high-throughput format. The invention provides methods for detecting proliferation of a mixture of cell types in a culture, for screening a library of compounds to identify those compounds that modulate proliferation of a cell, and for detecting the presence or absence of targets in a sample. The invention also provides kits comprising at least first polynucleotide tag and a second polynucleotide tag.

Abstract: The present invention relates to immunosuppressant, process for their production, their uses and pharmaceutical compositions containing them. The invention provides a novel class of compounds useful in the treatment or prevention of diseases or disorders mediated by lymphocyte interactions, particularly diseases associated with EDG receptor mediated signal transduction.

Abstract: This invention provides novel methods and compositions for modulating T cell differentiation and T cell responses. The modulators are identified by screening test compounds for ability to modulate an inositol 1,4,5-trisphosphate 3-kinase (IP3K). The IP3K modulators can be further examined for their activity in modulating development of progenitor T cells (e.g., CD4+/CD8+ double positive T cells) into mature CD4+ or CD8+ single positive T cells. Pharmaceutical compositions comprising these T cell modulators can be administered to a subject to modulate T cell immune responses, to suppress inflammations, and to treat disease conditions such as autoimmune diseases, graft rejection or allergies.

Abstract: The present invention relates to bicyclic derivatives, process for their production, their uses and pharmaceutical compositions containing them. The invention provides a novel class of compounds useful in the treatment or prevention of diseases or disorders mediated by lymphocyte interactions, particularly diseases associated with EDG/S1P receptor mediated signal transduction.

Abstract: The invention provides methods for inhibiting stem cell differentiation and for increasing the effective dose of stem cells in a subject. HSC differentiation can be inhibited by applying an HSC differentiation-inhibiting polypeptide identified in the present invention to an HSC culture in vitro, or administering the polypeptide to a subject in vivo. Some other methods of the invention comprise first obtaining a population of hematopoietic stem cells, introducing into the cells an HSC differentiation-inhibiting polynucleotide disclosed herein, and expressing the HSC differentiation-inhibiting polynucleotide in the cells. Such genetically modified stem cells can be administered to a subject whereby effective dose of the stem cells in the subject can be increased. This invention further provides novel molecular markers of hematopoietic stem cells, and methods for enriching hematopoietic stem cells using these novel markers.

Abstract: This invention provides novel AP-1 modulatory polypeptides. The invention also provides methods for screening modulators of AP-1 transcription factor activities. The methods comprise first screening test agents for modulators of an AP-1-modulatory polypeptide and then further screening the identified modulating agents for modulators of AP-1 transcription factor activities. The invention further provides methods and pharmaceutical compositions for modulating AP-1 transcription factor activities in a cell and for treating diseases and conditions mediated by abnormal cellular proliferation.

Abstract: The invention is directed to novel biaryl derivatives, to the uses of these compounds in various medicinal applications, including the treatment, prevention and control of proliferative diseases such as tumors, and to pharmaceutical compositions comprising these compounds. Compounds of the invention can be used to treat or prevent diseases or disorders that involve the activity of MIF-1 and/or adenosine kinase.