30 results about "Integrin ligand" patented technology

The present invention provides α4β1 integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.

The present invention relates to integrin ligand modified long circulation liposome carrying anticarcinogen for injection, and is especially one kind of injected anticarcinogen carrying targeting liposome administration system. The efficient administration system is obtained through modifying the surface of liposome simultaneously with both polyethylene glycol and integrin containing arginine-glycine-asparagic acid sequence or RGD analogue.

The present invention provides α4β1 integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.

Antagonists of alpha 4 integrin / alpha 4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are useful in suppressing bone destruction associated with multiple myeloma. The homing of multiple myeloma cells to bone marrow and their alpha 4 integrin-dependent release of bone-resorbing factors, resulting in bone destruction in patients with multiple myeloma, is inhibited.

The invention relates to a cyclopeptide analog and a cyclization method thereof, which aims at providing an integrin ligand cyclopeptide analog and a cyclization method thereof. The cyclization method comprises the following steps: Azido-glycine is firstly generated by glycin with the effects of trifluoromethanesulfonic anhydride and Sodium azide; Fmoc-Asp-Propargyl is then generated by condensation with propargylamine in solution; after side-chain carboxyl of propargyl acyl aspartic acid is then hung on 2-CTC resin, linear tetrapeptide analogs are condensed in turn, and the linear tetrapeptide analogs are then cut down from the resin; and the cyclopeptide analog is synthesized in the condition of liquid phase (DCM is used as a solvent and CuBr / DBU is used as catalyst) after 4 to 6 hours of reaction at room temperature. The cyclopeptide analog and cyclization method has the following advantages: (1) the integrin ligand cyclopeptide analog in the invention is introduced with heterocyclic rings (triazole rings), thereby being capable of increasing biological activity; and (2) the cyclization method in the invention is more simple, convenient and high-efficient, and the condition is moderate.

Provided is a fusion protein comprising a tumor necrosis factor related apoptosis inducing ligand (TRAIL), integrin ligands of αVβ3 and αVβ5 and a linking peptide. Also provided are the expression method and simple separation and purification process for the production of the fusion protein which is soluble and has high content of the polymer, and use of the fusion protein for the manufacturing of a medicament for the treatment of tumor. The fusion protein has good tumor tissue targeting property, significantly enhanced anti-tumor effect, which can also reduce the dose of the needed protein for the target treatment effect, improve the bioavailability, reduce the treatment cost, decrease and overcome the potential toxic and side effects of the tumor necrosis factor-related apoptosis inducing ligand.

The present invention discloses an integrin blocking agent polypeptide and applications of the same in preparation of drugs for treatment of neovascular eye diseases, and belongs to the field of medicine. The integrin blocking agent polypeptide comprises a polypeptide I Arg-Gly-Asp-Gly-Gly-Gly-Gly-Phe- Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala and a polypeptide II Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Al a-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Gly-Gly-Gly-Gly-Arg-Gly-Asp, wherein the polypeptide I is modified with the integrin ligand sequence (Arg-Gly-Asp-Gly-Gly-Gly-Gly). The integrin blocking agent polypeptide can be used for treatments of iridal neovascular eye diseases, choroidal neovascular eye diseases, retinal neovascular eye diseases or corneal neovascular eye diseases and other neovascular eye diseases.

Vascular endothelial growth factor and type I collagen inducible protein (VCIP), also known as phosphatidic acid phosphatase 2b (PAP2b), was identified in a functional assay of angiogenesis. Previously, VCIP was not known to function as an integrin ligand. The present invention discloses VCIP-derived peptides and proteins act as integrin ligands. Since VCIP-derived peptides or proteins are capable of inhibiting specific cell-cell interactions, such inhibitors of cell-cell interactions would be useful for developing novel therapeutic approaches to treat diseases where these interactions have clear pathological consequences. For example, VCIP / PAP2b can be a novel target for anti-angiogenic, anti-cancer and anti-metastatic therapy.

The present invention provides α4β1 integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.

The invention discloses an application of a blocker with integrin affinity and bonding capability and MMPs (matrix metalloproteinases) inhibiting capability, and belongs to the field of medicines. The application comprises a polypeptide I (Arg-Gly-Asp-Gly-Gly-Gly-Gly-Pro-(D-Pyr)-(D-Cys)-Bip-Arg-Gly-Glu) and a polypeptide II (Pro-(D-Pyr)-(D-Cys)-Bip-Arg-Gly-Glu-Gly-Gly-Gly-Gly-Arg-Gly-Asp), wherein the polypeptide I is modified with an integrin ligand sequence (Arg-Gly-Asp-Gly-Gly-Gly-Gly); two types of blood vessel inhibiting polypeptides with integrin affinity and bonding capability are formed. The application has the advantages that because of the targeting property of an RGD (arginine-glycin-aspartate) sequence, the polypeptides can be targeted to the new blood vessel endothelium of the RA (rheumatoid arthritis) pannus forming process, the forming of MMPs (matrix metalloproteinases) and the new blood vessel can be inhibited, and the effect of preventing or treating the blood vessel and inflammatory diseases are realized; the polypeptides can be applied to the treatment of the blood vessel and inflammatory diseases, such as arthritis, inflammation, tumors, and eye diseases.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising the continuous administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agent or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy.

The present invention provides α4β1 integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered together with said ligands, such as chemotherapeutic agents and / or radiation therapy, in isolated organ perfusion. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.

Small molecule integrin ligand mimetics facilitate integrin-ligand interactions, which may be used to prepare vaccines, adoptive cell therapies, immunotherapies for cancer, and a variety of other conditions. As integrin mediated cell-cell interactions are critical to antigen presentation and effector cell killing, increasing the efficiency of integrin receptor-ligand interactions will stabilize the immune synapse and improve effector functions. Compositions and methods including the mimetics enhance: (1) the priming of vaccines (including, but not limited to, cancer vaccines); (2) cytolytic activity of adoptive cell therapies (including, but not limited to γδT-cells, CTLs, NK, iNKT); (3) immunotherapies (including, but not limited to, negative checkpoint blockage strategies such as anti-CTLA-4 and anti-PD-1); and (4) biologic therapies (including, but not limited, to trastuzumab and rituxamab), whereby the mechanism-of-action includes antibody dependent cellular cytotoxicity (ADCC).

Provided is a fusion protein comprising a tumor necrosis factor related apoptosis inducing ligand (TRAIL), integrin ligands of αVβ3 and αVβ5 and a linking peptide. Also provided are the expression method and simple separation and purification process for the production of the fusion protein which is soluble and has high content of the polymer, and use of the fusion protein for the manufacturing of a medicament for the treatment of tumor. The fusion protein has good tumor tissue targeting property, significantly enhanced anti-tumor effect, which can also reduce the dose of the needed protein for the target treatment effect, improve the bioavailability, reduce the treatment cost, decrease and overcome the potential toxic and side effects of the tumor necrosis factor-related apoptosis inducing ligand.

The present invention is directed to modified integrin proteins and methods and compositions using integrin-based therapeutics. In one embodiment, the modified integrins demonstrate increased occurrence or duration of the E−H+ integrin protein conformation. In another embodiment, the compounds of the present invention stabilize E−H+ integrin protein conformation, increasing the occurrence or duration of the E−H+ integrin protein conformation. In another embodiment, the compounds of the present invention inhibit binding of a ligand of an integrin. In yet a further embodiment, the present compounds increase cis binding of the integrin or signaling based thereon. The present compounds decrease the occurrence or duration of trans binding of the integrin or signaling based thereon. The modified integrins and compounds described herein may be used in methods of treating immune modulated diseases or inflammatory diseases or conditions.

Small molecule integrin ligand mimetics facilitate integrin-ligand interactions, which may be used to prepare vaccines, adoptive cell therapies, immunotherapies for cancer, and a variety of other conditions. As integrin mediated cell-cell interactions are critical to antigen presentation and effector cell killing, increasing the efficiency of integrin receptor-ligand interactions will stabilize the immune synapse and improve effector functions. Compositions and methods including the mimetics enhance: (1) the priming of vaccines (including, but not limited to, cancer vaccines); (2) cytolytic activity of adoptive cell therapies (including, but not limited to γδT-cells, CTLs, NK, iNKT); (3) immunotherapies (including, but not limited to, negative checkpoint blockage strategies such as anti-CTLA-4 and anti-PD-1); and (4) biologic therapies (including, but not limited, to trastuzumab and rituxamab), whereby the mechanism-of-action includes antibody dependent cellular cytotoxicity (ADCC).

The present invention belongs to the field of pharmacy and relates to a highly stable multifunctional short peptide mn having high affinity with integrin and multi-functions of targeting tumor neovascularization, tumor mimic blood vessels and tumor cells, a polypeptide-modified complex, a drug delivery system and uses of the short peptide mn in preparation of drugs for tumor diagnosis and treatment. Experiment results show that mn-modified drugs are specifically taken up by integrin-expressing positive cells and tumor tissue, and have good tumor targeting and imaging functions; and a drug delivery system constructed by an mn-modified polymer carrier material effectively delivers entrapped drugs to target tissue and significantly improves the tumor diagnosis and treatment. Comparing the prepared drugs with widely used integrin ligand c (RGDyK), the mn has better stability in serum and stronger binding ability with the integrin, immunogenicity of a modified carrier system is significantly lower than a carrier system modified by the c (RGDyK), etc., mn-mediated in-vivo active targeting drug delivery effects are more effective and the mn has good application prospects in the tumor diagnosis and targeted therapy.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered together with said ligands, such as chemotherapeutic agents and / or radiation therapy, in isolated organ perfusion. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone.

The invention discloses an application of a blocker with integrin affinity and bonding capability and MMPs (matrix metalloproteinases) inhibiting capability, and belongs to the field of medicines. The application comprises a polypeptide I (Arg-Gly-Asp-Gly-Gly-Gly-Gly-Pro-(D-Pyr)-(D-Cys)-Bip-Arg-Gly-Glu) and a polypeptide II (Pro-(D-Pyr)-(D-Cys)-Bip-Arg-Gly-Glu-Gly-Gly-Gly-Gly-Arg-Gly-Asp), wherein the polypeptide I is modified with an integrin ligand sequence (Arg-Gly-Asp-Gly-Gly-Gly-Gly); two types of blood vessel inhibiting polypeptides with integrin affinity and bonding capability are formed. The application has the advantages that because of the targeting property of an RGD (arginine-glycin-aspartate) sequence, the polypeptides can be targeted to the new blood vessel endothelium of the RA (rheumatoid arthritis) pannus forming process, the forming of MMPs (matrix metalloproteinases) and the new blood vessel can be inhibited, and the effect of preventing or treating the blood vessel and inflammatory diseases are realized; the polypeptides can be applied to the treatment of the blood vessel and inflammatory diseases, such as arthritis, inflammation, tumors, and eye diseases.

The invention discloses a research method for restraining porcine epidemic diarrhea virus infection based on integrin ligand recognition peptides. The method comprises the following steps of S1, diluting a Vero E6 cell suspension, and placing the diluted Vero E6 cell suspension in a cell culture incubator for culturing; S2, when cell density achieves 90%, removing a culture medium, and performingmoistening; S3, adding the cells to a basic culture medium containing the integrin ligand recognition peptides, and performing hatching; S4, after the liquid is removed, adding virus maintaining liquid; S5, performing inoculating with porcine epidemic diarrhea viruses; S6, after the Vero E6 cells inoculated with the viruses are placed in the cell culture incubator for 2h, sucking liquid; S7, adding the virus maintaining liquid, and placing mixed liquid in the cell culture incubator for culturing; S8, storing cells; S9, collecting samples, and performing real-time fluorescent quantitation PCR;S10, collecting samples, and performing western blotting; and S11, counting research results. The research method can verify whether the integrin ligand recognition peptides est, com and er have the effect of resisting PEDV infection, and reference is provided for prevention and control of PED and development of antiviral drugs.

The invention belongs to the technology field of a tumor targeting and slow release drug delivery system, and relates to a drug-carrying tumor targeting cationic polymer. The surface of the cationic polymer is modified by linear chain or cyclic polypeptide containing RGD sequence to obtain a series of cationic polymers. The obtained cationic polymers can be used for the preparation of anticancer drug-carrying nano-particle drug-delivery system. The nano-particle slow release in combination with tumor targeting effect of RGD increases accumulation of the anticancer drug in tumor part and inhibits tumor growth by breaking tumor new vessels to improve drug curative effect.

The present invention relates to integrin ligand modified long circulation liposome carrying anticarcinogen for injection, and is especially one kind of injected anticarcinogen carrying targeting liposome administration system. The efficient administration system is obtained through modifying the surface of liposome simultaneously with both polyethylene glycol and integrin containing arginine-glycine-asparagic acid sequence or RGD analogue.