31 results about "Calcineurin" patented technology

This invention relates to a method of treating transplant rejection comprising administering to a patient a pharmaceutical composition comprising an lck inhibitor and a calcineurin inhibitor or an immunosuppressant.

The present invention provides methods of treating and preventing cardiac hypertrophy and heart failure. MEF-2, NF-AT3, calcineurin, MCIP, and Class II HDACs have been shown to have a major role in cardiac hypertrophy and heart disease, and inhibition of many of these factors or the pathways mediated by these factors has been shown to have a beneficial, anti-hypertrophic effect. The present invention provides a link between these factors and the pathways they mediate through a family of non-voltage gated channels called TRP channels. The present invention further demonstrates that inhibitors of TRP channels can inhibit or treat heart failure and cardiac hypertrophy.

In accordance with the present invention, it has been discovered that glucose and incretin hormones promote pancreatic islet cell survival via the calcium and cAMP dependent induction, respectively, of the transcription factor CREB. Specifically, a signaling module has been identified which mediates cooperative effects of calcium and cAMP on islet cell gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a cytoplasmic CREB coactivator. The module comprises a cAMP regulated snf1-like kinase called SIK2 and the calcium regulated phosphatase calcineurin, both of which associate with TORC2 in the cytoplasm. TORC2 is repressed under basal conditions through a phosphorylation dependent interaction with 14-3-3 proteins. cAMP and calcium signals stimulate CREB target gene expression via complementary effects on TORC2 dephosphorylation; cAMP disrupts TORC2-associated activity of SIK2 or related family members, whereas calcium induces TORC2 dephosphorylation via calcineurin. These findings provide a novel mechanism by which CREB activates cellular gene expression, depending on nutrient and energy status, and facilitate development of assays to identify compounds which modulate the role of TORCs. In accordance with the present invention, it has been discovered that fasting and energy-sensing pathways regulate the gluconeogenic program in liver by modulating the nuclear entry of a transcriptional coactivator called Transducer of Regulated CREB Activity 2 (TORC2). Hepatic TORC2 over-expression induces fasting hyperglycemia, whereas knockdown of TORC2 leads to fasting hypoglycemia and silencing of the gluconeogenic program. Since a majority of individuals with Type II diabetes exhibit fasting hyperglycemia due to elevated hepatic gluconeogenesis, compounds that enhance TORC2 phosphorylation will find use as therapeutic agents in this setting.

The invention discloses a calcineurin catalytic subunit gene which is cloned in a cryptococcus humicolus BSLL1-1 strain. The nucleotide sequence of the calcineurin catalytic subunit gene is shown in SEQ ID NO:1 and is used for coding the protein with an amino acid sequence shown in SEQ ID NO:2; the protein is expressed in escherichia coli, and the calcineurin catalytic subunit gene is further successfully expressed in saccharomyces cerevisiae. According to the calcineurin catalytic subunit gene, the saccharomyces cerevisiae is enhanced in aluminum resistant capacity, genetically engineered bacteria are capable of adsorbing (or absorbing) activated aluminum contained in a culture medium, and the genetically engineered bacteria of the saccharomyces cerevisiae have application prospect of reducing the content of activated aluminum contained in acid soil.

The embodiments disclosed herein relate to ophthalmic compositions comprising calcineurin inhibitors or mTOR inhibitors, and more particularly to methods for treating an ocular disease and / or condition using the disclosed compositions. According to aspects illustrated herein, there is provided a pharmaceutical composition that includes a calcineurin inhibitor or an mTOR inhibitor; a first surfactant with an HLB index greater than about 10; and a second surfactant with an HLB index of greater than about 13, wherein an absolute difference between the HLB index of the first surfactant and the HLB index of the second surfactant is greater than about 3, and wherein the composition forms mixed micelles.

The present invention concerns methods of treating fungal infections and methods of screening compounds for activity in treating fungal infections. Methods of the invention include using an active compound such as fludioxonil to treat a Cryptococcus neoformans infection. Also included are methods and pharmaceutical compositions useful for treating fungal infections using a Hog1 activator such as fludioxonil and a calcineurin inhibitor in combination.

Disclosed is an inhibitor of calcineurin of the setron family for use for treating hearing loss in a subject in need thereof.

Described are novel means in the treatment of cerebral neurological conditions such as ischemic insult of the brain. Furthermore, a kit for a non-radioactive protein serine / threonine phosphatase activity assay is provided, which is capable of detecting and distinguishing the activity of PP1, PP2A, and calcineurin (PP2B).

The present invention relates to compositions and methods for reducing the risk and / or extent of radiocontrast-induced nephropathy (“RIN”) for kidney-imaging procedures that employ a radiocontrast medium. It is based, at least in part, on the discovery that, in a renal tubular cell line, radiocontrast induced inflammatory upregulation and cell injury could be reduced by calcineurin inhibitors FK506 and cyclosporine.

The present invention relates to a composition for preventing or treating transplantation rejection or a transplantation rejection disease, comprising a novel compound and a calcineurin inhibitor. A co-administration of the present invention 1) reduces the activity of pathogenic Th1 cells or Th17 cells, 2) increases the activity of Treg cells, 3) has an inhibitory effect against side effects, such as tissue damage, occurring in the sole administration thereof, 4) inhibits various pathogenic pathways, 5) inhibits the cell death of inflammatory cells, and 6) increases the activity of mitochondria, in an in vivo or in vitro allogenic model, a transplantation rejection disease model, a skin transplantation model, and a liver-transplanted patient, and thus inhibits transplantation rejection along with mitigating side effects possibly occurring in the administration of a conventional immunosuppressant alone. Thus, the present invention may be used in the field of pharmaceutics relating to transplantation rejection or various immune disorders possibly occurring after transplantation.

Provided herein are antibodies, or antigen-binding portions thereof, which specifically bind to pathologic forms of calcineurin. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and methods for use of these antibodies.

The present invention provides the use of a peptide comprising an amino acid sequence of SEQ ID NO:3, or the encoding nucleic acid thereof, for manufacturing medicament for treatment of diseases associated with increased NF-κB activity. The peptide can interact with IKB and influence phosphorylation of IKB in the tyrosine at position 42, thereby inhibiting the signal pathway of NF-κB.

Compositions targeting sperm calcineurin may be used as topical and reversible contraceptives. The compositions may include calcineurin inhibitors such as tacrolimus (e.g. FK506) and / or Cyclosporin A. The compositions may be gels, creams, or lotion-based formulations and may be used reversibly and locally for both males and females.

The present invention provides a medicament for improving or preventing a symptom relating to a retina and / or light reception, the medicament comprising, as an active ingredient, a substance capable of maintaining or enhancing the phosphorylation state of Unc119; a method for screening for a substance capable of improving or preventing a symptom relating to a retina and / or light reception, the method comprising the step of selecting a substance capable of inhibiting calcineurin, or selecting a substance capable of activating casein kinase 2; and an agent for inhibiting retinal degeneration and an agent for protecting a retina, the agents each comprising, as an active ingredient, a substance capable of maintaining or enhancing the phosphorylation state of Unc119.

The present invention relates to a method for diagnosing susceptibility for a myocardial and / or immunological disorder, a kit and a therapeutic agent comprising a peptide of SEQ ID NO: 1 or 2 and uses thereof.

The invention relates to an alkyl and heterocyclic compound serving as a hepatitis-c-virus inhibitor and application of the alkyl and heterocyclic compound in medicine. Particularly, the invention discloses a compound which is shown in a formula (I) and can be used for the hepatitis-c-virus inhibitor, or discloses an optical isomer of the compound or a pharmaceutically acceptable salt and water compound or a solvate. The compound can be used for treating hepatitis c virus (HCV) infection or hepatitis c disease, and can also serve as a HCV non-structural 5A (NS5A) calcineurin inhibitor.

Provided is a method of inhibiting the growth of a fungus using eltrombopag, wherein the fungus is selected from the group consisting of Cryptococcus, Candida glabrata, and Trichophyton rubrum. Also provided are a combination agent that includes eltrombopag and a macrolide calcineurin inhibitor and a method of using the combination agent for inhibiting the growth of Cryptococcus. Also provided is a method of inhibiting virulence factor formation in Cryptococcus using eltrombopag.

A method is described for inducing the formation of cementum and a periodontal ligament between a dental implant and bone by administering cementum attachment protein (CAP) together with a calcineurin inhibitor such as cyclosporin A (CSA). Also contemplated is an implant kit comprising a titanium or other biologically inert dental or orthopedic implant and a coating of CAP and a calcineurin inhibitor such as CSA. Furthermore, application of CAP and CSA to dental root surfaces can be used to induce the regeneration of a periodontal ligament during treatment for periodontal disease. A similar method for reattaching a fibrous structure, such as a tendon, ligament or joint capsule, to bone is described.

The invention discloses a pharmaceutical composition for treating nephrotic syndrome. The pharmaceutical composition comprises glucocorticoid, a calcineurin inhibitor, mycophenolic acid, or a pharmaceutically acceptable salt and prodrug of mycophenolic acid. The pharmaceutical composition not only can play a role in multiple links of immunosuppression in a process of treating nephrotic syndrome, especially idiopathic membranous nephropathy and achieve a better effect through synergism of drug effects, but also can obviously reduce the dosage of each drug and reduce respective adverse reactionsand toxic and side effects.

The present invention relates to a composition comprising secreted extracellular vesicles (SEV) of cells expressing nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4(NFATC4), for use in the treatment of cancer or in the treatment or prevention of metastatic cancer. It further relates to in vitromethods for determining or predicting the therapeutic efficiency of a treatment with a composition comprising SEV of cells expressing NFATC4 in a cancer patient, based on the ability of the composition comprising SEV of cells expressing NFATC4 to induce an increase in TGFβ1 expression level.