66 results about "Constitutively active" patented technology

The present invention relates to a method of identifying compounds which act as inverse agonists of the 5-HT2A receptor, the method comprising contacting a constitutively active 5-HT2A receptor with at least one test compound and determining any decrease in the level of basal activity of the receptor so as to identify a test compound which is an inverse agonist of the 5-HT2A receptor. Such inverse agonists may be used in the treatment of schizophrenia and related psychoses.

An isolated polynucleotide is disclosed comprising a nucleic acid sequence encoding a polypeptide having an amino acid sequence of HIF-1 alpha, the polypeptide being stably expressed and constitutively active. Isolated polypeptides encoded by same are also disclosed and uses thereof.

The present invention includes a method of inhibiting or reducing deregulated FLT3 tyrosine kinase activity or FLT3 tyrosine kinase expression in a subject with a proliferative disease by administering to the subject having or suspected to have the proliferative disease, a therapeutically or prophylactically effective amount of the compound of Formula I:or pharmaceutically acceptable salt thereof.

The present invention relates to inhibitors of progastrin induced repression of ICAT for treating and / or preventing colorectal cancer, adenomatous polyposis or metastasis displaying progastrin-secreting cells and cells in which the beta-catenin / Tcf-4-mediated transcriptional pathway is constitutively active.

Compounds of the invention act as inverse agonist ghrelin receptors. Some of the compounds of the invention may have both inverse agonistic and antagonistic properties as they both decrease or eliminate the constitutive activity of he ghrelin receptor and block the effect of ghrelin. Other preferred compounds of the invention have inverse agonistic properties but have little or no antagonistic activity. The compounds are suitable for medical and / or cosmetic use in connection with modulation of feeding behaviors, body composition and reduction of body mass. The invention also relates to methods for identifying inverse agonists for the ghrelin receptor and for monitoring the further development of such compounds.

With the current invention, we provide new methods of enhancing the T-cell stimulatory capacity of human dendritic cells (DCs) and their use in cancer vaccination. The method comprises the introduction of different molecular adjuvants to human DCs through transfection with at least two mRNA or DNA molecules encoding markers selected from the group of: CD40L, CD70, constitutively active TLR4 (caTLR4), IL-12p70, EL-selectin, CCR7 and / or 4-1 BBL; or in combination with inhibition of SOCS, A20, PD-L1 and / or STAT3 expression, for example through siRNA transfection. We could show a clear increase in the immunostimulatory capacity of DCs obtained in this way, enabling them to elicit an unexpectedly high T-cell immune response in vitro. Introduction of at least two of the above molecules, in combination with a tumor-specific antigen enables the DCs to elicit a significant host-mediated T-cell immune response in vivo against the tumor antigen and thus makes them very attractive in the manufacturing of anti-cancer vaccines.

The invention describes the use of dendritic cell vaccines, wherein SHP-1 expression or activity is modulated in the dendritic cell. In particular, the invention provides dendritic cells (DC) transduced with an SHP1-shRNA adenovirus, or dominant negative (dn-SHP-1) or constitutively active (ca-SHP-1), and pulsed with an antigen. The methods and compositions of the invention are used for the prevention and / or treatment of cancers, other cell proliferation diseases and conditions, diseases caused by a pathogen, or autoimmune disorders.

An isolated polynucleotide is disclosed comprising a nucleic acid sequence encoding a polypeptide having an amino acid sequence of HIF-1alpha, the polypeptide being stably expressed and constitutively active. Isolated polypeptides encoded by same are also disclosed and uses thereof.

Provided are methods and compositions for maintaining the viability of photoreceptor cells following retinal detachment. The viability of photoreceptor cells can be preserved by administering a neuroprotective agent, for example, a substance capable of suppressing endogenous calcineurin or constitutively active calcineurin, inhibiting cleavage of calcineurin to constitutively active calcineurin, and / or directly or indirectly antagonizing calcineurin or constitutively active calcineurin (and combinations thereof), to a mammal having an eye with retinal detachment. The neuroprotective agent maintains the viability of the photoreceptor cells until such time that the retina becomes reattached to the underlying retinal pigment epithelium and choroid. The treatment minimizes the loss of vision, which otherwise may occur as a result of retinal detachment.

The invention relates to a recombinant adeno-associated virus vector. The recombinant adeno-associated virus vector comprises constitutively active human Nrf2 (Nrf2 (CA)), a CMV promoter / enhancer, beta-globin intron for increasing gene expression, human growth hormone poly (A) tail sequence, etc. The invention also relates to a preparation method of the recombinant adeno-associated virus vector and the application of the recombinant adeno-associated virus vector or a composition containing the recombinant adeno-associated virus vector in preparing a medicine for treating glaucoma retinal ganglion cell denaturation. The recombinant adeno-associated virus vector provided by the invention can obviously reduce the intraocular pressure of a mouse, increase the survival rate of RGCs of the mouse, and effectively treat glaucoma retinal ganglion cell pathological changes.

Currently no therapies that provide either protection or restoration of neuronal function for adult onset neurodegenerative diseases such as Parkinson's disease exist. Many clinical efforts to provide such benefits by infusion of neurotropic factors have failed. An alternative approach such as viral construct transduction may be used to directly activate the intracellular signaling pathways that mediate neurotrophic effects and induce axon growth. Viral construct transduction of dopaminergic neurons with a constitutively active human form of the p70S6K gene—hp70S6K (CA)—was shown to induce axon regeneration from living dopaminergic cell bodies that had no living axons.

Disclosed is a complete plant MAP kinase cascade (e.g., MEKK1, MKK4 / MKK5, and MPK3 / MPK6) and WRKY22 / WRKY29 transcription factors that function downstream of the flagellin receptor FLS2, a leucine-rich-repeat (LRR) receptor kinase. Activation of such a MAPK cascade confers resistance to both bacterial and fungal pathogens. Also disclosed are disease-resistant plants expressing one or more members of this MAP kinase signaling cascade. Such members include constitutively active MEKK1 (ΔMEKK1), MKK4 (MKK4a), and MKK5 (MKK5a) or wild-type WRKY29.

The present invention features mammalian expression systems with improved production yields, and method of using these systems to produce desired proteins. In one embodiment, the expression systems of the present invention comprise genetically-engineered mammalian host cells cultured in a medium that contains an effective amount of heparin or heparin-like molecules. The presence of heparin or heparin-like molecules significantly increases protein production by the cultured cells. The present invention also features the use of constitutively-active components of FGFR-I-mediated signal transduction pathways to improve protein production by cultured mammalian cells. Co-expression of such a component with a protein of interest markedly increases the production yield of the protein of interest.

The subject invention concerns materials and methods for inhibiting the Akt / PKB pathway. In one embodiment, a compound of the invention inhibits kinase activity and / or phosphorylation levels of Akt proteins. The subject invention also concerns methods for inhibiting or killing a cancer cell or other cell in which expression of an Akt protein is elevated or constitutively active, comprising contacting the cell with an effective amount of a compound of formula I. The subject invention also concerns methods for treating cancer or a tumor in a person or animal comprising administering an effective amount of a compound of formula I to the person or animal.

The present invention relates to the constitutive activity of the Hedgehog pathway in non-small cell lung carcinoma (NSCLC). A method for diagnosing NSCLC by detecting the level of a component of the Hedgehog pathway is provided, as is a method for identifying subjects that will respond positively to treatment with a Hedgehog pathway antagonist. Methods for treating subjects with cancer or cancers resistant to Hedgehog pathway antagonists are also provided.

Non-native constitutively phosphorylated forms of osteopontin are disclosed. Such osteopontin forms can be obtained, for example, using an expression vector comprising an isolated nucleic acid that encodes an osteopontin peptide, operably linked to a promoter wherein the osteopontin peptide is either constitutively phosphorylated or is capable of being constitutively phosphorylated. Also disclosed are mutant osteopontin peptides that are either constitutively phosphorylated, or are capable of being constitutively phosphorylated. The disclosed osteopontin forms have anti-calcification activity and, therefore, numerous applications. They can be used, for example, to create calcification-resistant tissue, or to treat calcification-related disease.

All multiple myeloma cell lines examined showed constitutively active IκB kinase (IKK), IκBα phosphorylation and constitutively active NF-κB. Curcumin, a chemopreventive agent, suppressed constitutive IκBα phosphorylation through inhibition of IKK activity and downregulated NF-κB. Curcumin also downregulated expression of NF-κB-regulated gene products such as IκBα, Bcl-2, Bcl-xL, cyclin D1 and interleukin-6. Consequently, curcumin suppressed multiple myeloma cell proliferation and arrested cells at the G1 / S phase of the cell cycle. Curcumin also induced apoptosis and chemosensitivity to vincristine. Overall, results presented herein provide a molecular basis for the treatment of multiple myeloma patients with this pharmacologically safe agent.

All multiple myeloma cell lines examined showed constitutively active IκB kinase (IKK), IκBα phosphorylation and constitutively active NF-κB. Curcumin, a chemopreventive agent, suppressed constitutive IκBα phosphorylation through inhibition of IKK activity and downregulated NF-κB. Curcumin also downregulated expression of NF-κB-regulated gene products such as IκBα, Bcl-2, Bcl-xL, cyclin D1 and interleukin-6. Consequently, curcumin suppressed multiple myeloma cell proliferation and arrested cells at the G1 / S phase of the cell cycle. Curcumin also induced apoptosis and chemosensitivity to vincristine. Overall, results presented herein provide a molecular basis for the treatment of multiple myeloma patients with this pharmacologically safe agent.

Provided are methods and compositions for maintaining the viability of photoreceptor cells following retinal detachment. The viability of photoreceptor cells can be preserved by administering a neuroprotective agent, for example, a substance capable of suppressing endogenous calcineurin or constitutively active calcineurin, inhibiting cleavage of calcineurin to constitutively active calcineurin, and / or directly or indirectly antagonizing calcineurin or constitutively active calcineurin (and combinations thereof), to a mammal having an eye with retinal detachment. The neuroprotective agent maintains the viability of the photoreceptor cells until such time that the retina becomes reattached to the underlying retinal pigment epithelium and choroid. The treatment minimizes the loss of vision, which otherwise may occur as a result of retinal detachment.

The present invention features mammalian expression systems with improved production yields, and method of using these systems to produce desired proteins. In one embodiment, the expression systems of the present invention comprise genetically-engineered mammalian host cells cultured in a medium that contains an effective amount of heparin or heparin-like molecules. The presence of heparin or heparin-like molecules significantly increases protein production by the cultured cells. The present invention also features the use of constitutively-active components of FGFR-I -mediated signal transduction pathways to improve protein production by cultured mammalian cells. Co-expression of such a component with a protein of interest markedly increases the production yield of the protein of interest.

The invention is directed to a method for identifying substances acting as ligands for transfected receptors by using transfected markers to measure receptor / ligand interactions. The present invention also relates to a method of identifying compounds which act as inverse agonists of the 5-HT2A receptor, the method comprising contacting a constitutively active 5-HT2A receptor with at least one test compound and determining any decrease in the amount of basal activity of the receptor so as to identify a test compound which is an inverse agonist of the 5-HT2A receptor. Such inverse agonists may be used in the treatment of schizophrenia and related psychoses.

Disclosed is a method for post-translational modification of a recombinant protein in a cell-free expression system. The method comprises co-expressing the enzyme responsible for the post-translational modification along with the target protein in a prokaryotic based in vitro expression system. In one embodiment the expression system further comprises a eukaryotic cell extract, and in an alternative embodiment the target protein is co-expressed with a modified kinase that is constitutively active. In particular, a method for post-translational modification of a highly active MAPK 14 is described.

The present invention features compositions and methods for effectively altering PUFA content in animal cells, i.e., cells other than C. elegans, such as cells of birds or fish, such as muscle cells, nerve cells ( in the peripheral or central nervous system), adipocytes, endothelial cells, and cancer cells, the composition includes a nucleic acid encoding fat-1, which is optionally and operably linked to a persistently active or tissue-specific promoter or Other regulatory sequences, and pharmaceutically acceptable formulations with nucleic acids or biologically active variants thereof. The compositions and methods include a modified fat-1 gene, wherein the gene contains at least one optimized codon. The modified cells, whether in vivo or in vitro (i.e., in tissue culture), transgenic animals (especially fish and birds) comprising these modified cells, and food obtained from those animals (also That is, meat or other edible parts of animals (ie, liver, kidney or pancreas) are also included within the scope of the present invention.

Disclosed is a complete plant MAP kinase cascade (e.g., MEKK1, MKK4 / MKK5, and MPK3 / MPK6) and WRKY22 / WRKY29 transcription factors that function downstream of the flagellin receptor FLS2, a leucine-rich-repeat (LRR) receptor kinase. Activation of such a MAPK cascade confers resistance to both bacterial and fungal pathogens. Also disclosed are disease-resistant plants expressing one or more members of this MAP kinase signaling cascade. Such members include constitutively active MEKK1 (ΔMEKK1), MKK4 (MKK4a), and MKK5 (MKK5a) or wild-type WRKY29.

The invention relates to an enveloped microorganism in whose genome the following components are inserted and can be expressed: I) a nucleotide sequence that encodes a directly or indirectly, antiproliferatively or cytotoxically active expression product or a plurality of said expression products, II) a nucleotide sequence that encodes or is constitutively active for a blood plasma protein under the control of a activation sequence that can be activated in the microorganism, III) optionally, a nucleotide sequence that encodes or is constitutively active for a cell-specific ligand under the control of an activation sequence that can be activated in the microorganism, IV) a nucleotide sequence for a transport system that induces expression of the expression products of components I) and II) and optionally III) on the outer surface of the microorganism or that induces secretion of the expression products of component I) and expression of component II) and optionally component III) and that is preferably constitutively active, V) optionally a nucleotide sequence for a protein used for lysis of the microorganism in the cytosol of mammalian cells and for the intracellular release of plasmids with at least one or more components I) and VI) contained in the lysed microorganism, and VI) an activation sequence that can be activated in the microorganism, and / or that is tissue-specific, tumor cell-specific, function-specific or not cell-specific, for expressing component I). The inventive microorganism is further characterized in that any of components I) to VI) can be present either single or several times, and can be either identical or different.