14 results about "SH2 domain" patented technology

Provided are a biosensor for detecting Csk kinase activity in cells and a detection method thereof, relating to the technical field of biosensors. The biosensor fuses N-terminal ECFP, an SH2 domain of Src, a flexible linker having 15 amino acids, a substrate polypeptide, and C-terminal YPet; the substrate polypeptide is selected from one of a Src kinase C-terminal tail peptide chain FTSTEPQYQPGENL, a Fyn kinase C-terminal tail peptide chain FTATEPQYQPGENL, and a Csk specific substrate peptide EEEIYFFF. An FRET biosensor provided by the present invention and relating to a fluorescence resonance energy transfer (FRET) technology and gene encoding provides a powerful tool for visualizing signal molecules in living cells with high temporal-spatial resolution, can specifically visualize the dynamic state of the Csk kinase in the cells, and provides a visualization tool for further exploring the action mechanism of in-vivo Csk.

The invention belongs to the technical field of biological medicines, and particularly relates to a long-acting STAT3 inhibition polypeptide and application thereof in tumor resistance. The long-acting STAT3 inhibition polypeptide is designed by taking an SH2 structural domain in a negative regulatory protein SH2 adapter protein F (Shf) of STAT3 protein as a template and combining single-point mutation and active fragment splicing and N-terminal long-acting fatty acid chain modification, the tumor inhibition effect is enhanced while template targeted affinity STAT3 protein and high selectivity to tumor cells are reserved, and the tumor inhibition effect is improved. Meanwhile, the plasma stability is enhanced, the half-life period is prolonged, and the bioavailability is improved. The long-acting STAT3 inhibitory polypeptide provided by the invention is stable in chemical property and relatively low in toxicity to normal cells, and has potential anti-tumor clinical application value and wide development prospect.

This application discloses a SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) inhibitor and a Polo-like kinase I (PLK1) inhibitor for use in medicine, in particular for use in the treatment of cancer, more in particular of oesophageal cancer and colorectal cancer. Also disclosed is a kit of parts comprising a SHIP2 inhibitor and a PLK1 inhibitor for use in the treatment of cancer. Further disclosed are a kit of parts comprising a dosage form of a SHIP2 inhibitor and a dosage form of a PLK1 inhibitor and a pharmaceutical composition comprising a SHIP2 inhibitor and a PLK1 inhibitor.

The application discloses a salicylaldehyde derivative and application thereof. The compound and pharmaceutically acceptable salt and ester thereof can inhibit the combination of STAT3 and phosphorylated polypeptide, and achieve the anti-tumor purpose. The salicylaldehyde derivative can be combined with the SH2 domain of target protein STAT3, and inhibit the combination of the target protein and phosphorylated polypeptide. Compound 25 shows good competitive inhibition activity. In the anti-proliferation activity of pancreatic cancer cells in vitro, the compound 25 has sub-micromolar anti-proliferation activity of pancreatic cancer cells, and can induce cancer cell apoptosis. In addition, the compound 25 can significantly inhibit the phosphorylation of STAT3 705 sites and 727 sites, can inhibit the proliferation of various tumor cells in vitro, and has low toxicity to normal cells. Therefore, the compound can be used for preparing a STAT3 inhibitor, and used for preparing a medicine for preventing and / or treating diseases related to tumors.

The application belongs to the technical field of biological medicine, and particularly relates to the use of SH2 domain-containing protein tyrosine phosphatase 1 (SHP1) in the preparation of a drug for treating chronic pain, in particular to the use of SHP1 in the preparation of a drug for treating chronic pain by regulating the morphology of spinal cord astrocytes, the integrity of the blood-spinal cord barrier and the STAT1-CXCL10-CXCR3 neuroimmune signal axis, and a chronic pain treatment strategy based on the signal axis. The application first discloses that SHP1 in spinal cord astrocytes directly dephosphorylates STAT1, inhibits the transcription of CXCL10 and the subsequent infiltration of T lymphocytes into the spinal cord, and discloses the core analgesic mechanism, thereby establishing SHP1 as a new target for treating chronic pain, and opening up a new way for the precise treatment of clinical chronic pain, especially neuropathic pain.

The present invention relates to a cell which comprises a chimeric antigen receptor (CAR) and a signal transduction modifying protein, selected from one of the following: (i) a truncated protein which comprises an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM), but lacks a kinase domain; (ii) a truncated protein which comprises an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based inhibition motif (ITIM) but lacks a phosphatase domain; (iii) a fusion protein which comprises (a) an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) or from a protein which binds a phosphorylated immunoreceptor tyrosine-based inhibition motif (ITIM); and (ii) a heterologous domain.

The invention discloses a biomolecule and protein directed evolution system and method. According to the invention, an SH2 structural domain of Grb2 is connected with affibody in series, 13 sites of the affibody in biomolecules obtained through series connection are mutated, an M13 phage display library is established, and then screening is carried out to find that the SH2 structural domain of Grb2 is connected with affibody in series, and then the affibody in the biomolecules is subjected to directed evolution, so that a mutant which not only retains the binding characteristic of Grb2 but also has improved affinity to pYxNx peptide can be obtained. Therefore, the invention provides a protein directed evolution system and method capable of improving the affinity of the protein without influencing the binding characteristics of the protein, and the method has the advantages of relatively simple operation, low cost and the like, and is beneficial to the research of the interaction relationship between the proteins and the development of antibody drugs and the like.

Provided are an anti-tumor fusion protein, a preparation method therefor and an application thereof. Specifically, the fusion protein contacts a CPP element, an optional linking element, and a SH2 domain of SHP2 or SHP1 or an active fragment thereof. The obtained fusion protein has an extremely excellent anti-tumor effect.

A method for assessing susceptibility of cell lung cancer cells to a tyrosine kinase inhibitor, a method for preparing lung cancer cells resistant to a tyrosine kinase inhibitor, and a method for assessing an epidermal growth factor receptor tyrosine kinase activity of lung cancer cells. The methods use a reagent suitable for measuring an epidermal growth factor receptor tyrosine kinase activity and that contains: a modified polypeptide to which an acceptor and a donor inducing Förster resonance energy transfer are bound, and which includes CrkL, a CrkL fragment retaining an SH2 domain and a portion subjected to phosphorylation by a tyrosine kinase, or a CrkL variant that has an amino acid sequence having an identity of 90% or more with respect to an amino acid sequence of CrkL or the CrkL fragment and that becomes a substrate for a tyrosine kinase; or a nucleic acid encoding the modified polypeptide.

Provided herein are allosteric compounds, inhibitors or inhibitor compounds selective for the kinase domain or the non-kinase domains Jak3-SH2 or FERM-SH2 in the Jak3 enzyme. Also provided are methods for treating a breast cancer, such as a triple negative breast cancer and it brain metastases, for preventing or reducing the likelihood of the triple negative brain cancer metastasizing, and for inhibiting the proliferation of cancer cells from, for example, a breast cancer, a uterine cancer and an ovarian cancer or their metastases.

The present disclosure provides for high affinity variants of SH2 domains, methods of manufacturing such compositions, their use in screening, and in methods of their administration. The compositions and methods provided herein can be used for targeting protein phosphorylation of tyrosine residues as a means for identifying markers of pathology for therapeutic interventions.

The invention discloses a screening method of a small molecule STAT3 inhibitor and application of the small molecule STAT3 inhibitor. The screening method comprises the following steps: obtaining an STAT3 protein-small molecule compound crystal structure from a Protein Data Bank database, and carrying out pretreatment on the STAT3 protein-small molecule compound crystal structure; a SiteMap module is adopted to search a protein surface binding pocket, and a pocket at an SH2 structural domain is selected to screen an STAT3 inhibitor; selecting the center of a butt joint box and setting the size of the butt joint box; selecting and downloading a to-be-screened compound library; compound library preprocessing, multi-mode molecular docking and MM / GBSA free energy calculation are performed in sequence in a virtual screening workflow mode, and sorting is performed according to combination free energy values from small to large; and a molecular dynamics simulation method of Binding Pose Metadynamics is adopted for further screening, so that a compound with potential activity is obtained.

A modular biosensor (pYtags) for receptor tyrosine kinase activity may be provided, along with systems and techniques incorporating such biosensors. pYtags may include a cell surface receptor, such as a receptor tyrosine kinase (RTK), modified with a tyrosine activation motif that, when phosphorylated, recruits, e.g., a fluorescently labeled tandem SH2 domain with high specificity. Orthogonal pYtags can be used to monitor the dynamics of, e.g., EGFR and ErbB2 activity in the same cell, revealing distinct phases of activation for each RTK.

The invention discloses a compound and application thereof, and the compound can be combined with an SH2 structural domain of a target protein STAT3 to inhibit the combination of the target protein and phosphorylated polypeptide so as to achieve the anti-tumor purpose. Pharmacological experiments prove that the compound disclosed by the invention achieves the anti-tumor purpose by inhibiting proliferation of tumor cells and inducing apoptosis of the tumor cells. The compound provided by the invention can be used for preparing STAT3 inhibitors and medicines for preventing and / or treating tumor-related diseases.