6 results about "SH2 domain" patented technology

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.

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.

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.