36 results about "Αvβ3 integrin" patented technology

The present invention discloses a RGD-labeled fluorescent gold nano-cluster preparation method, which comprises: preparing gold nanoparticles with a particle size of less than 2 nm by using a BSA method; and carrying out an amidation reaction on the prepared gold nano-cluster and RGD having amino to obtain the RGD-labeled fluorescent gold nano-clusters. According to the present invention, the obtained gold nano-cluster (Au Nanoclusters, AuNCs) is the novel precious metal fluorescent nanometer material, and has characteristics of simple preparation conditions, simple preparation steps, near-infrared light emitting under a visible light source, small particle size, good monodispersity, good stability, low toxic-side effect, high safety, stable fluorescent property, and high CT imaging contrast resolution; a small amount of expression of integrin [alpha]v[beat]3 exists in most normal tissues and mature vascular endothelial cells while the over-expression of the integrin [alpha]v[beat]3 exists in a variety of cancer cells and neovessel endothelial cells, and the ligand is called RGD polypeptide sequence; and the RGD is selected as the targeting molecule, and the AuNCs and the RGD polypeptide sequence are conjugated to prepare the RGD-labeled fluorescent gold nano-cluster RGD-AuNCs@BSA.

Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin αvβ3 receptor-antagonist activity and substantially reduced integrin αllbβ3 and / or α5β1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin αllbβ3 and / or α5β1 as compared to a wild-type disintegrin. The variant is useful for treatment and / or prevention of αvβ3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.

A kind of amalgamation albumen combined peptide and hrn TNF specificity of the knub neconatal vein and its preparation method is disclosed in the invention. The knub necro-gene is a kind of multi-functional cell gene, which participates in immunity metabolizating modulation of the economy, has restriant and cell poison action to growth of some cancer cells. The invention wipes off 1-7 bit amino acid of the amido end of the knub necro-gene, changes 8-10 bit amino acid into Arg-Lys-Arg and 157 bit amino acid of carboxyl end into Phe, and composes new type high effect and low poison knub necro-gene nrhTNF. On the basis, prepared amalgamation albumen combined peptide and nrhTNF specificity ofthe knub neonatal vein can enrich at the place of knub neonated vein by use of the cyclopeptide CRGDC containing five amino acids elected from phage revelation library.

An aryl-substituted alicyclic compound of the formula (I):wherein U is 1,4,5,6-tetrahydropyrimidin-2-yl, etc., A is phenylene, etc., B is piperidine-1,4-diyl, etc., Z is —CONH—, etc., R3 is hydrogen, etc., R5 is hydrogen, aryl, etc., R6 is a mono-substituted amino (e,g., benzyloxycarbonylamino), R7 is hydrogen, etc., and a process for preparation thereof, and a pharmaceutical composition containing the same. The compound of the present invention has a high selectivity for αvβ3 integrin, and exhibits a potent inhibitory activity thereto, and hence, it is useful as a preventive or / and a therapeutic agent for a disease in which αvβ3 integrin is involved.

The present invention provides αVβ3 integrin cysteine loop domain agonists and antagonists (including peptide agonists and antagonists and analogs thereof), along with methods of using the same.

This invention relates to new peptide-based compounds and their use in therapeutically effective treatments as well as for diagnostic imaging techniques. More specifically the invention relates to the use of such peptide-based compounds used as targeting vectors that bind to receptors associated with angiogenesis, in particular the αvβ3 integrin receptor. Such contrast agents may thus be used for diagnosis of for example malignant diseases, heart diseases, inflammation-related diseases, rheumatoid arthritis and Kaposi's sarcoma. Moreover such compounds may also be used in therapeutic treatment of these diseases.

The present invention is drawn to cyclic RGD peptides linked via a disulfide bond, where the terminal cysteines are preferably in the D configuration. These peptides target αvβ3 integrin on tumor cells and neovasculatures and function as targeting agents for tumor diagnostic imaging and therapy. Compared with the commonly used RGD ligands, compounds of the present invention have improved targeting efficacy and lower nonspecific binding to normal organs. Moreover, the compounds of the present invention can be functionalized to conjugate imaging payload without decreasing binding strength.

Disclosed herein are peptides which include an isoDGR motif and which selectively inhibit αvβ3 integrin. In some embodiments, the isoDGR motif results from the deamidation of an NGR motif.

The present invention provides αVβ3 integrin cysteine loop domain agonists and antagonists (including peptide agonists and antagonists and analogs thereof), along with methods of using the same.

The invention provides disintegrin variants, and more specifically to disintegrin variants which are selective αvβ3 integrin antagonists for treatment and prevention of αvβ3 integrin-associated diseases. The present invention also relates to pegylated proteins, including proteins comprising a disintegrin variant having an RGD motif variant 48ARLDDL53. The invention also relates to the use of the polypeptides of the invention for the treatment and prevention of αvβ3 integrin-associated diseases.

This invention relates to new peptide-based compounds and their use in therapeutically effective treatments as well as for diagnostic imaging techniques. More specifically the invention relates to the use of such peptide-based compounds used as targeting vectors that bind to receptors associated with angiogenesis, in particular the alphavbeta3 integrin receptor. Such contrast agents may thus be used for diagnosis of for example malignant diseases, heart diseases, inflammation-related diseases, rheumatoid arthritis and Kaposi's sarcoma. Moreover such compounds may also be used in therapeutic treatment of these diseases.

The invention generally relates to fusion proteins comprising a rhodostomin variant having an RGD motif variant 48ARLDDL53, wherein the rhodostomin variant is conjugated with a variant of Human Serum Albumin (HSA). The invention also relates to the use of these fusion proteins for treatment and prevention of avss3 integrin-associated diseases.

The present invention relates to the use of a peptide that interacts with the αvβ3 integrin of endothelial cells. More particularly, the invention relates to a method for inhibiting endothelial cell adhesion, endothelial cell migration and / or angiogenesis, using a peptide consisting of at least 18 amino acids, comprising tyrosine-histidine (TY) or asparagines-histidine (NH), and at least three hydrophobic amino acids with bulky side chains; or equivalents thereof. Furthermore, the invention provides a method for treating or preventing angiogenesis-related diseases, using the peptide.

The invention discloses a polyester peptide vesicle with the inner membrane with negative charges and a preparation method and application of the polyester peptide vesicle, and belongs to the technical fields of high molecular materials and practical chemistry. The preparation method comprises the steps that a PEG-b-PAPA-b-PAsp tri-block polymer is simply prepared through NCA ring opening polymerization and deprotection, wherein cRGD-CLP obtained through preparation has the advantages of being small in size, good in stability and high in protein encapsulation amount; the cRGD-CLP (SAP-cRGD-CLP) with soapwart toxin proteins can be specifically targeted to alphavbeta3 integrin overe-xpressed tumor cells, and shows high cytotoxicity to A549 lung cancer cells. The cRGD-CLP can be long circulated in vivo, enrichment of a protein drug at the tumor site is further promoted, and in-situ A549 lung cancer growth is completely inhibited. Therefore, the vesicle is easily prepared, the protein loading capacity is high, the tumor targeting ability is high, and the polyester peptide vesicle has a great potential in protein treatment of tumors.

The invention discloses a class of aminocyanine fluorescent dyes linked to the cyclic peptide cyclo (RGD) and its preparation method and application. The general structural formula of the compound is as I; it is composed of structural units II and III; the structural unit II is a derived cyanine dye Structure, belonging to water-soluble fluorescent molecules, its spectrum has a large Stokes shift, and is less toxic to normal cells; structural unit III is a cyclic peptide structure of a specific ligand for αvβ3 integrin receptors, which can be used for targeting position. The fluorescent dye has dual functions of tumor imaging diagnosis and targeted therapy.

Disclosed herein is a bispecific peptide conjugate comprising an epidermal growth factor receptor (EGFR) targeting peptide, an αvβ3 integrin targeting peptide, and a linker, where the linker is conjugated respectively to the EGFR targeting peptide and the αvβ3 integrin targeting peptide.

The invention discloses a USPIO-PLA-RGD compound, a preparation method and application thereof. The USPIO-PLA-RGD compound uses USPIO as a core, is coated by PLA outside, and is labeled as PLA-USPIO; and the USPIO-PLA-GRD compound obtained through covalently coupling carboxyl of a functional group exposed on the surface of PLA and amidogen of RGD peptide has a hydrated grain diameter of between 90 and 105 nm. The USPIO-PLA-RGD compound can be applied as magnetic resonance tumor angiogenesis targeting contrast agent. The invention realizes targeting developing by the characteristics of high affinity of an alpha v beta3 integrin receptor and ligand RGD peptide thereof, and the combination has the characteristics of high specificity, selectivity, saturation and affinity, clear biological effect and the like. The concentration of a medicament in a partial focus can be increased, and toxic and side effects can be reduced by using the ligand RGD peptide as a vector of USPIO through the mediation effect of the receptor, so that the aim of development of a targeting tumor angiogenesis living body is realized.

The invention discloses a nanometer drug of dendrobetin with a small particle size targeting αvβ3 integrin receptor highly expressed tumor cells and a preparation method thereof. The mass ratio of the raw material drug to the carrier is 1:10-1:100, and the carrier includes an amphiphilic polymer and a targeting compound, wherein the molar ratio of the amphiphilic polymer to the targeting compound is 1:100-1: 1. The carrier is a micelle carrier, the surface of which is modified with a high-affinity ligand of the αvβ3 integrin receptor overexpressed on the surface of tumor cells. The invention realizes that the drug can actively target specific tumor cells and can make the drug fast and effective Being taken up by cells, the drug can exert anti-tumor effect to a greater extent, and reduce the distribution of the drug in the whole body and the resulting toxic and side effects.

Novel antibodies directed against Dual Ig domain containing cell adhesion molecule (DICAM) are described. These anti-DICAM antibodies are capable of detecting DICAM by Western blot and / or flow cytometry, blocking the interaction between DICAM and its ligand αVβ3 integrin, and / or blocking the migration of inflammatory cytokine-secreting TH17 lymphocytes across the blood brain barrier. Uses of these antibodies or compositions comprising same for the diagnosis, prevention and / or treatment of autoimmune / inflammatory conditions, such as neuroinflammatory conditions, and for the targeting, identification and selection of inflammatory cytokine-secreting TH17 lymphocytes or precursor thereof are also disclosed.