191 results about "Vascular Endothelial Growth Factor Receptor" patented technology

The present invention concerns methods and reagents useful in modulating vascular endothelial growth factor (VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D) and / or vascular endothelial growth factor receptor (e.g., VEGFR1, VEGFR2 and / or VEGFr3) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against VEGF and / or VEGFr gene expression and / or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of VEGF and / or VEGFr expression or activity.

The present disclosure relates to novel vascular endothelial growth factor receptor (VEGFR)-binding polypeptides and methods for using these polypeptides to inhibit biological activities mediated by vascular endothelial growth factors (VEGFs). The present disclosure also provides various improvements relating to single domain binding polypeptides.

The current invention provides a method for mobilising endothelial progenitor cells (EPC) and / or mesenchymal stem cells (MSC) in a patient, wherein the method comprises the steps of (i) administering a vascular endothelial growth factor receptor (VEGFR) agonist to the patient; and (ii) administering an antagonist of CXCR4 to the patient. Also provided are uses of EPC and MSC harvested using the methods of the invention.

Bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity are provided in the present invention. The compositions of the present invention possess dual activity in a single agent of potent vascular endothelial growth factor receptor inhibitory activity as well as antitubulin activity. Water soluble salts of these compositions are also described. Methods of treating a patient having cancer, macular degeneration, and arthritis with the compositions and salts thereof of the present invention are disclosed.

The present invention concerns methods and reagents useful in modulating vascular endothelial growth factor (VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D) and / or vascular endothelial growth factor receptor (e.g., VEGFR1, VEGFR2 and / or VEGFr3) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (mRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against VEGF and / or VEGFr gene expression and / or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of VEGF and / or VEGFr expression or activity.

The present invention relates to binding proteins specific for Vascular Endothelial Growth Factor A (VEGF-A), in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx (wherein xxx denotes the amino acid length of the VEGF-A mature protein) binding to Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.

Method of treating persons having carcinoma, sarcoma or hematopoietic cancer by administering (i) a compound of the formula (I)and (ii) an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor receptor (VEGFR) inhibitor and pharmaceutical compositions for use in said method. A method for treating gastric cancer, colon cancer, lung cancer, breast cancer, pancreas cancer, kidney cancer, prostate cancer, medulloblastoma, rhabdomyosarcoma, Ewing sarcoma, liposarcoma, multiple myeloma and leukemia by administering a compound of the formula (I).

A cell-based screen is reported can be used to identify specific receptor-binding compounds in a combinatorial library of peptoids (N-alkylglycine oligomers) displayed on beads. This strategy was applied to the isolation of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2)-binding peptoids, which were optimized to create lead compounds with high affinity for VEGFR2. One of these peptoids was shown to be an antagonist of VEGF-VEGFR2 interaction and receptor function.

The present invention relates to human monoclonal antibodies neutralizing vascular endothelial growth factor receptor and the use thereof. More specifically, relates to human ScFv molecules neutralizing vascular endothelial growth factor receptor, and a composition for inhibiting angiogenesis and a composition for treating cancer, which contain the human ScFv molecules. The disclosed monoclonal antibody neutralizing vascular endothelial growth factor receptor shows excellent neutralizing ability in living cells, compared to that of a commercially available antibody against vascular endothelial growth factor receptor, and shows the ability to neutralize vascular endothelial growth factor receptor not only in humans, but also in mice and rats. Thus, the monoclonal antibody will be useful in anticancer studies and will be highly effective in cancer treatment.

An objective of the present invention is to provide a newly isolated vascular endothelial growth factor (VEGF)-like protein having binding activity specific to a vascular endothelial growth factor receptor type 2 (KDR) but exhibiting no binding affinity to a vascular endothelial growth factor receptor type 1 (Flt-1), and thus being excellent in hypotensive effect. There have been newly purified and isolated a VEGF-like protein from a venom of Vipera ammodytes ammodytes: vammin and a VEGF-like protein from a venom of Daboia russelli russelli: VR-1 as the VEGF-like protein having binding activity specific to KDR but exhibiting no binding affinity to Flt-1, and thereby being excellent in hypotensive effect, and the amino acid sequences of these both have been analyzed in the present invention.

Method of treating persons having carcinoma, sarcoma or hematopoietic cancer by administering (i) a compound of the formula (I)and (ii) an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor receptor (VEGFR) inhibitor and pharmaceutical compositions for use in said method. A method for treating gastric cancer, colon cancer, lung cancer, breast cancer, pancreas cancer, kidney cancer, prostate cancer, medulloblastoma, rhabdomyosarcoma, Ewing sarcoma, liposarcoma, multiple myeloma and leukemia by administering a compound of the formula (I).

The invention discloses a soluble VEGFR (Vascular Endothelial Growth Factor Receptor) difunctional chimera receptor VEGFR31-Ig as well as a preparation method and application thereof in preparing antineoplastic drugs. The soluble VEGFR difunctional chimera receptor VEGFR31-Ig disclosed by the invention can not only be combined with VEGF-A and VEGF-B, but also be combined with VEGF-C or VEGF-D, and can be used for preparing the antineoplastic drugs.

The invention belongs to the technical field of genetically engineered antibody, in particular relates to a fusion protein of tumor vascular endothelial growth factor receptor 2 (VEGFR2 / KDR3) antibody and MICA as well as a preparation method and use thereof. In the invention, a full-length antibody of VEGFR2 is linked with a ligand MHC I molecule associated protein A (MICA) of activated receptor of NK cell (NKG2D) through a flexible linker and expressed by CHO cells by utilizing the genetic engineering technology, and the formed fusion protein can act on VEGFR on the surface of a tumor cell to inhibit or kill tumor and inhibit or destroy tumor angiogenesis, and on the other hand, the formed fusion protein can increase the level of MICA on the surface of the tumor cell and stimulate the NK cells to kill tumor cells through identification of NKG2D on the surfaces of the NK cells, thereby reestablishing the immunological surveillance of an body activated by the NKG2D pathway, and enhancing effects of antibody-dependent cell-mediated cytotoxicity (ADCC) and the like mediated by the Fc region of the antibody to kill tumor cells.

The invention relates to production of a genetic engineering drug by a recombinant DNA technology, belongs to the biotechnical field, and particularly relates to a purification method of a recombinant human vascular endothelial growth factor receptor-antibody fusion protein, that is to say, a cell supernatant containing the recombinant human vascular endothelial growth factor receptor-antibody fusion protein is successively subjected to affinity chromatography, anion exchange chromatography, cation exchange chromatography, hydrophobic chromatography and desalination chromatography to obtain the high-quality recombinant human vascular endothelial growth factor receptor-antibody fusion protein. The purification method has the characteristics of low cost, high purity of the target protein, easily controlled technological process, easily large-scale enlarged production and the like.

The invention belongs to the technical field of genetic engineering antibodies and particularly relates to a whole human source single chain antibody which is designed and expressed by genetic engineering and has specific affinity towards human vascular endothelial growth factor receptor 2 (VEGFR-2). The invention also provides a nucleotide sequence of heavy chain variable region and light chain variable region immunoglobulin molecules, a nucleotide sequence which comprises the heavy chain variable region and light chain variable region immunoglobulin molecules, an amino acid sequence which comprises variable heavy chain and variable light chain immunoglobulin molecules, and a sequence which corresponds to CDR1, CDR2 and CDR3 of a complementary determining region. The invention also provides a method for generating and expressing the anti-VEGFR-2 single chain antibody, by cycling operations of gathering-elution-gathering, an antibody which has specific affinity towards the human vascular endothelial growth factor is screened, and then the single chain antibody is obtained through a prokaryotic cell secretion and expression system and an affinity purification system. The antibody can be coupled with a detectable substance and therapeutic agent.

The invention relates to the technical field of biomedicine, in particular to an improved anti-VEGFR (vascular endothelial growth factor receptor)-2 monoclonal antibody and application. On the basis of the original research, a new phage antibody library is designed by computer-aided simulation by taking two of them with the highest affinity as templates, and improved heavy chain variable region and light chain variable region amino acid sequences are obtained by multi-round screening; the affinity and biological activity of the anti-VEGFR 2 monoclonal antibody are higher than those of the original antibody. The anti-VEGFR 2 monoclonal antibody obtained by the invention has relatively high affinity, can inhibit the binding of VEGFR-2 and a ligand VEGF thereof in vitro and has good biological activity, and can be used for the treatment of tumors, macular degeneration and other diseases caused by neovascularization.

The invention belongs to the field of antibody drug, and discloses a full human-derived anti-human VEGFR2 monoclonal antibody screened by a phage antibody base technology and prepared by a gene engineering method, and further discloses a carrier including polynucleotide for encoding the monoclonal antibody, a host cell and an application. Through combining with VEGFR2, the monoclonal antibody stops the combination of VEGF with VEGR2, and does not induce receptor dimerization, cause the following tyrosine residue phosphorylation in intracellular tyrosine kinase structure and activate downstream signal access including activation of phospholipase C and increase of calcium ion concentration in the cell and others; the antibody drug triggers endothelial proliferation, survival, cytoskeleton rearrangement, cell migration, gene expression and others, and finally stops the vascular proliferation caused by combination of VEGF and VEGFR2 and induction of dimerization. The monoclonal antibody can be used for treating diseases caused by tumor angiogenesis.

The invention discloses Lactobacillus plantarum with a colorectal cancer inhibition function and an application of the Lactobacillus plantarum and belongs to the technical field of microorganisms. TheLactobacillus plantarum CCFM164 with the preservation number being CGMCC No.14520 can tolerate gastric acid and cholate, remarkably relieve inflammatory response at a colorectal part of a colorectalcancer model mouse, and tumor quantity of the colorectal part of the model mouse is reduced by regulating Notch1 and Notch2 signaling pathways in colorectal tissue and expression of VEGFR2 (vascular endothelial growth factor receptor 2) molecules. Besides, the Lactobacillus plantarum CCFM164 can improve intestinal flora structure and short-chain fatty acid level in the intestinal tract. The Lactobacillus plantarum CCFM164 can be used for preparing fermented food capable of inhibiting colorectal cancer and has quite extensive application prospect.

The invention discloses a thienopyrimidine and furopyrimidine derivative, its preparation method and its application in medicines. The derivative is a compound shown as general formula I, general formula II, general formula III or general formula IV. The thienopyrimidine and furopyrimidine pyrimidine derivative provided in the invention has an obvious EGFR (epidermal growth factor receptor) inhibitory activity, and some of the compounds also have an obvious inhibitory activity on VEGFR (vascular endothelial growth factor receptor), so that the thienopyrimidine and furopyrimidine pyrimidine derivative can be expected to be developed into tyrosine kinase EGFR or / and VEGFR inhibitors, which can be used for preparation of drugs preventing or treating diseases related to EGFR and / or VEGFR. Therefore, the derivative provided in the invention provides a new development direction and approach for developing novel tyrosine kinase inhibitor drugs that have low resistance or can alleviate early inhibitor resistance, and has wide application prospect and medicinal value.

The invention relates to the fields of pharmaceutical chemistry and organic chemistry, in particular to isoquinolinone derivatives. The compounds can be used for treating various medical indications associated with postmenopausal symptoms, uterine fiber lesions and arterial smooth muscle cell proliferation, particularly ER-(+) breast cancer by inhibiting alpha-estrogen receptor subtype (ER alpha) and through vascular endothelial growth factor receptor (VEGFR-2) bi-target. Meanwhile, the compounds have an obvious inhibiting effect on tumor metastasis, and have a general formula I.

The present invention relates to the field of eye drops and particularly relates to a nanocrystalline eye drop, and a preparation method and an application thereof. The nanocrystalline eye drop comprises double-soluble macromolecules, single-soluble macromolecules and targeted drugs acting on vascular endothelial growth factor receptors and / or platelet growth factor receptors. The double-soluble macromolecules and the single-soluble macromolecules interact to encapsulate the targeted drugs to form nanocrystallines and maintain stability of the nanocrystallines. The eye drop can quickly penetrate a blood-eye barrier and enter a vitreous body through a special intercellular space penetration and / or pinocytosis method, an effective therapeutic effect is achieved through passive targeting andattachment, and at the same time, the drug is convenient to use.

The related chalketoxime shown as the formula (1) is prepared by heating and reflux reacting the 2', 4'-dihydroxy -6'-methoxyl-3', 5'-dimethylchalcone and hydroxylamine hydrochloride in pyridine, which has well solvability, fit to direct inject for drug, restrains obviously all of the activity of blood vessel endothelium growth factor receptor, HER2 receptor and Tyr kinase as PDGFR receptor, the external growth of cells for breast cancer and liver cancer, and the phosphorylation of KDR in ECV304 cell, HER2 in MDA-MB-453 cell and PDGFR receptor in C6 cell, and benefit to treat tumor.

The present invention describes an approach to cancer therapy utilizing novel VEGF receptor antagonists. Specifically, the invention provides peptides and polynucleotides encoding VEGF receptor antagonists and methods of use thereof.

The invention relates to a drug composition preparation for recombining human vascular endothelial growth factor receptor-antibody fusion protein and preparation thereof. The drug composition preparation specifically comprises recombination fusion protein, a buffering agent, a stabilizing agent, a surfactant and sterilize injection water. The drug composition preparation is capable of effectivelyinhibiting fusion protein accumulating and depositing, hydrolyzing, oxidizing, decarboxamidation and other side reaction, and meanwhile, the stability of the product in pressurizing (high temperature,strong light irradiating, freeze thawing, and the like), accelerating and long-term frozen storing conditions can be effectively improved; and the safety in clinical use can be improved.

The invention relates to the field of gene engineering, and particularly relates to an anti-VEGFR-1 (Vascular Endothelial Growth Factor Receptor-1) mosaic type antigen receptor and lymphocyte capable of expressing the antigen receptor, and aims at providing a new and effective choice for the technical field of antitumor. The technical scheme for solving the technical problems is as follows: a single-chain antibody ScFv is provided, the single-chain antibody can recognize VEGFR-1, the single-chain antibody is prepared into the mosaic type antigen receptor which has a structure of (ScFv-V)-(IgG1-Fc)-(CD4-TM)-(CD3-z), the encoding gene of the antigen receptor is transformed into a plasmid vector, and the plasmid vector is transfected to lymphocyte, so that the lymphocyte has antitumor action, thereby providing the new and effective choice for the field.

The present invention provides immunogenic peptides comprising the amino acid sequence of SEQ ID NO: 1, 2, 13, 32, and peptides comprising the above-mentioned amino acid sequences in which 1, 2, or several amino acids are substituted or added, and having cytotoxic T cell inducibility, and also provides drugs for treating or preventing tumors comprising these peptides. The peptides of this invention can be used as vaccines.

The invention relates to quinazolinyl aryl urea derivatives with a general formula I and a preparation method and application thereof, wherein R1, R2 and R3 respectively have meanings limited in a specification. The invention further relates to the preparation method of the derivatives, and a physiologically-acceptable salt formed by the derivatives and an inorganic acid or an organic acid includes a medicinal combination of the derivatives. The compounds have a valuable pharmacologic property, particularly have an inhibition effect on the signal transduction caused by a tyrosine kinase, particularly have higher inhibition activity on mutant VEGFR-2 (Vascular Endothelial Growth Factor Receptor-2), and furthermore, have lower toxicity. The invention further relates to the application of the quinazolinyl aryl urea derivatives in the treatment of diseases, particularly tumor diseases, and the preparation method of the quinazolinyl aryl urea derivatives.

The present disclosure relates to a recombinant adenovirus with improved angiogenesis inhibition activity and a pharmaceutical composition for inhibiting angiogenesis. The recombinant adenovirus includes: (a) an inverted terminal repeat (ITR) nucleotide sequence of an adenovirus; and (b) a nucleotide sequence coding for a chimeric decoy receptor containing (i) an extracellular domain of vascular endothelial growth factor receptor 1 (VEGFR-1) and (ii) an extracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The recombinant adenovirus according the present disclosure which expresses the chimeric decoy receptor inhibits angiogenesis very effectively and can be used for gene therapy for various angiogenesis-related diseases. Particularly, the recombinant adenovirus of the present disclosure has superior oncolytic activity.