37 results about "Αvβ3 integrin" patented technology

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.

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 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 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 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.