33 results about "Autophosphorylation" patented technology

An objective of the present invention is to provide novel compounds which have inhibitory activity against autophosphorylation of an FGF receptor family and, when orally or intraveneously administered, can suppress the growth of cancer cells. The compounds of the present invention are represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof:

wherein X represents CH or N; Z represents O or S; Q represents NR¹⁰, CR¹¹R², carbonyl, O, S(═O)m, wherein m is 0 to 2, or urea; R¹ to R³ each independently represent H, OH, halogen, nitro, amino, alkyl, alkoxy or the like in which the alkyl and alkoxy groups are optionally substituted; R⁴ represents H; R⁵ to R⁸ each independently represent H, halogen, alkyl, or alkoxy; and R⁹ represents an optionally substituted carbocyclic or heterocyclic group.

A class of compounds useful in pharmaceutical compositions and methods for treating or preventing cancer is described. The compounds' ability to inhibit RET kinase is quantified, i.e., their respective RET IC50 and EC50 values are described. One such compound, known as cyclobenzaprine and herein as SW-01, has been identified as RET-specific with an IC50 of 300 nM. SW-01 inhibits RET autophosphorylation and blocks the growth and transformation of thyroid cancer cell lines. It has been further tested in pancreatic cancer, breast cancer, and SCLC cell lines. The compounds show utility for inhibition of survival and proliferation of tumour cells.

The present invention relates to methods and compositions designed for the treatment, management, or prevention of a hypoproliferative cell disorder, especially those disorders relating to the destruction, shedding, or inadequate proliferation of epithelial and/or endothelial cells, particularly interstitial cystitis (IC) and lesions associated with inflammatory bowel disease (IBD). The methods of the invention comprise the administration of an effective amount of one or more agents that are antagonists of EphA2. In certain embodiments, the EphA2 antagonistic agent of the invention decreases EphA2-endogenous ligand binding, upregulates EphA2 gene expression and/or translation, increases EphA2 protein stability or protein accumulation, decreases EphA2 cytoplasmic tail phosphorylation, promotes EphA2 kinase activity (other than autophosphorylation or ligand-mediated EphA2 signaling), increases proliferation of EphA2 expressing cells, increases survival of EphA2 expressing cells, and/or maintains/reconstitutes epithelial and/or endothelial cell layer integrity. The invention also provides pharmaceutical compositions comprising one or more EphA2 antagonistic agents of the invention either alone or in combination with one or more other agents useful for therapy for a hypoproliferative cell disorder. Diagnostic methods and methods for screening for therapeutically useful agents are also provided.

α2-Heremans Schmid Glycoprotein (AHSG) inhibits insulin-induced autophosphorylation of the insulin receptor (IR) and IR-tyroskine kinase (TK) activity; genetic ablation of the Ahsg gene enhances insulin signal transduction and increase whole-body insulin sensitivity. Therefor, AHSG and its gene(s) are useful targets for agents that inhibit the development or progression of Type II diabetes or any disease or disorder associated with increased insulin resistance. Provided herein is a method for inhibiting the biological activity of AHSG protein in a cell using compounds that inhibit phosphorylation of AHSG. Also disclosed is a method of augmenting the phosphorylation or IR-TK activity in a liver or muscle cell by providing a compound that lowers the amount of active AHSG or inhibits the biological activity of AHSG. Such effects may be achieved by delivering an antisense nucleic acid construct that hybridizes with AHSG encoding DNA. This invention includes a method (a) treating a subject that is susceptible to, or suffers from, obesity and insulin resistance or (b) increasing insulin sensitivity, and thereby preventing or treating insulin resistance in the subject. The method comprises lowering the amount of active AHSG or inhibiting the biological activity of AHSG in the subject, preferably in liver or muscle, by using AHSG antisense constructs or an anti-AHSG antibody. In a subject eating a high fat diet, the effect on body weight gain and/or insulin resistance is diminished, and total body fat content is lowered, by lowering the amount of active AHSG or inhibiting the action of the AHSG in the subject using the agents noted above.

There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof:

wherein R¹ and R² represent hydrogen, alkyl or the like; R³, R⁴, R⁵, and R⁶ represent hydrogen, halogen, alkyl, alkoxy or the like; R¹¹ and R¹² represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R³, R⁴, R⁵ and R⁶ represent hydrogen and A represents group (v) wherein u is 0 (zero) and R¹⁹ represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.

The subject invention concerns peptide molecules that specifically inhibit the enzymatic function of tyrosine kinases, including the JAK and EGF receptor (EGFR) family of kinases, to autophosphorylate, i.e., to transfer a phosphate group from ATP to an amino acid in the kinase. Phosphorylation of proteins is the most fundamental method for signal transduction among proteins in a cell. Inhibition of tyrosine kinase autophosphorylation activities inhibits the enzyme's signaling and shuts down the functioning pathways originating from the enzyme. The JAK2 and EGFR tyrosine kinases are involved in both inflammatory disorders and cancer. In these disorders, the tyrosine kinases can often be activated in an uncontrolled fashion. The subject application also concerns antibodies that bind to a tyrosine kinase autophosphorylation site. The subject invention also concerns pharmaceutically acceptable formulations of the subject peptides and antibodies, and methods for treating inflammatory and oncological disorders by inhibiting tyrosine kinase signaling in these situations by administering a peptide or antibody of the present invention.

Disclosed herein are compositions and methods useful for promoting sperm motility, promoting embryonic stem cell formation, promoting trophoblast formation, or promoting neuronal growth. The compositions and methods are based on peptide sequences that bind trophinin, inhibit bystin-mediated arrest of epidermal growth factor (EGF) receptor, and promotes EGF receptor autophosphorylation.

The invention discloses a plant stress tolerance related protein GmTPRPK1, an encoding gene thereof, and an application thereof. The protein provided by the invention is (a) or (b): (a) the protein is composed of an amino acid sequence represented by a sequence 1 in a sequence listing; and (b) the protein which is related to the plant stress tolerance, derived from the sequence 1, and obtained through substituting and/or deleting and/or adding to the amino acid sequence of the sequence 1 by one or some amino acid residues. The GmTPRPK1 expresses under the induction of drought, high salt, ABA,ethylene and the like, and the expression of the GmTPRPK1 is inhibited under the low temperature threat. The GmTPRPK1 can enhance the resistance of a plant to high salt and drought, and the growth ofroots. The GmTPRPK1 allows autophosphorylation to be carried out, and can be positioned on nucleuses and cell membranes, and the distribution range is large. The GmTPRPK1 of the present invention lays the foundation for artificially controlling the expression of the anti-stress and stress resistance related gene, and plays an important role in breeding plant varieties with strengthened anti-stress and stress resistance.

The invention belongs to the technical field of medicine and relates to a targeted peptide of epidermal growth factor receptor (EGFR) and the application thereof. The design of the invention comes from small peptides of EY1068ING (sequence (SEQ) identity (ID) NO:1), PDY1148QQD (SEQ ID NO:2) and AEY1173LR(SEQ ID NO:3) of main self-phosphorylation acting site of EGFR. The peptide is used for modifying nanometer lipid carriers which comprise solid-state lipid material, lipid-state oil, fat-soluble emulsifier, polyethylene glycol (PEG) modified lipid, water-soluble emulsifier and additive. The peptide has the following characteristics: (1) the obtained polypeptide has small molecular weight, convenient synthesis, low cost, high affinity with EGFR and strong specificity; (2) the obtained small peptides has good EGFR targeting and can be used for constructing the carriers for targeted therapy of tumor with high expression of EGFR.

The identification and use of two major DNA-PKcs autophosphorylation sites. Threonine (T) 2609 and Serine (S) 2056, including antibodies specific for phosphorylated T2609 and 52056. Peptides and polynucleotides encoding same, that feature these two sites of phosphorylation. The antibodies do not bind to the unphosphorylated DNA-PKcs protein or peptide, thus providing diagnostic tools to monitor the effectiveness of treatments which target the DNA repair pathway of cancer cells, and the ability to intervene or inhibit in phosphorylation of T2609 or 52056, either through application of a drug or an antibody, to increase the radiosensitivity of cancer cells.

Object of the present invention is to provide a peptide functioning as a c-Met agonist. The present invention provides a peptide complex comprising two or more peptides that bind to a c-Met protein and a linker that links the two or more peptides to one another. Such a peptide complex promotes autophosphorylation of the c-Met protein and induces cell growth.

The present invention provides a method for screening compounds for their ability to inhibit autophosphorylation of Janus kinase 3 in the absence of any additional substrate. The present invention also provides a method for screening compounds that bind to Janus kinase 3 domains other than the kinase domain, to identify synthetic or natural compounds including biomolecules, that modulate Janus kinase 3 activity. This invention also describes a multi-component screening kit composed of purified recombinant Janus kinase 3 proteins and recombinant phosphorylated Janus kinase 3 fusion proteins including, one or more phosphorylated or non-phosphorylated domain-deleted Janus kinase 3 fusion proteins.

The present invention relates to nucleotide sequences, including expressed sequence tags (ESTs), oligonucleotide probes, polypeptides, vectors and host cells expressing, and immunoadhesions and antibodies to mammalian GFRα3, a novel α-subunit receptor of the GDNF (i.e. GFR) receptor family. It further relates to an assay for measuring activation of an α-subunit receptor by detecting tyrosine kinase receptor activation (i.e., autophosphorylation) or other activities related to ligand-induced α-subunit receptor homo-dimerization or homo-oligomerization.

The present invention relates to a package of screening methods for developing drugs against pathogenic microbes having two-component system of DevR-DevS and/or DevR-Rv2027c and its homologues, said method comprising steps of over-expressing DevR, DevS, and Rv2027c and their single domain derivatives including mutant variant proteins, autophosphorylating DevS, and Rv2027c proteins and thereafter, phosphotransfering to DevR and its derivatives in SDS-PAGE or High-throughput format in the presence of a test compound, and determining the drug-potential of the test compound, wherein the potential of the drug is inversely proportional to (i) the degree of autophosphorylation of DevS and Rv2027c, (ii). the degree of phosphotransfer-based dephosphorylation of DevR and/its single domain derivative, and (iii). the degree of dephosphorylation of phosphorylated species of DevS and Rv2027c and/their single domain derivatives, and a method of treatment, and a composition thereof.

Method, kit and composition for measuring the autophosphorylation of one or more tyrosine kinases in presence of a kinase inhibitor compared to the absence of said kinase inhibitor for kinase specificity profiling of kinase inhibitors.

The invention belongs to the field of biology, and in particular relates to application of a compound Ochrephilone in preparing an anti-tuberculosis medicine. The compound Ochrephilone belongs to the family of natural toxins. Researches discover than the compound Ochrephilone has autophosphorylation activity of mycobacterium tuberculosis serine/serine-threonine kinase G, so that the Ochrephilone can be used for preparing a new anti-tuberculosis medicine by using mycobacterium tuberculosis serine/serine-threonine kinase G as a target.

Hypoxia induced mitogenic factor (HIMF) is a member of the “found in inflammatory zone” (FIZZ)/resistin family of proteins and has potent mitogenic, angiogenic, and vasoconstrictive effects in the lung vasculature. The receptor/binding partners for this family of proteins have been largely unknown. We identified Bruton's tyrosine kinase (BTK) as a functional HIMF binding partner through GST-HIMF pull-downs and mass spectrometry. Using primary cultured HIMF-stimulated murine bone marrow cells, we demonstrated that BTK was recruited to the leading edge of the cells. We also demonstrated that BTK and the closely related tyrosine kinase Fyn, colocalized at the growth cone process in these cells. HIMF stimulation induced BTK autophosphorylation, which peaked at 2.5 minutes. A transwell migration assay showed that treatment with recombinant murine HIMF induced migration of primary cultured bone marrow cells, which was completely blocked by the BTK inhibitor, LFM-A13. In vivo studies, using the rat hindlimb ischemia model, revealed that HIMF can stimulate angiogenesis in the hypoxic tissue probably through inducing the migration of endothelial progenitor cells (EPCs) to areas of active angiogenesis. Our results indicate that HIMF may acts as a chemotactic molecule in stimulating the migration of leukocytes/EPCs from bone marrow to targeted tissues through activation of the BTK pathway.