49 results about "Integrelin" patented technology

This invention discloses the application of integrin αv inhibitors combined with γ-secretase inhibitors in the preparation of drugs for treating tumors. The study found that the combined use of integrin αv inhibitors and γ-secretase inhibitors in tumor treatment exhibits a synergistic effect, not only inhibiting in situ tumor growth but also significantly suppressing tumor invasion, distant metastasis, and other malignant progression, thus helping to slow tumor progression, improve treatment efficacy, and enhance patient prognosis. Furthermore, the study found that the combined use of integrin αv inhibitors and γ-secretase inhibitors can reduce the production of the intracellular free domain of integrin αv and inhibit the activation of the classical downstream pathway of integrin αv. The combined use of integrin αv inhibitors and γ-secretase inhibitors shows broad application prospects in tumor treatment.

Novel compounds that act as inhibitors of alpha4beta7 integrin are disclosed. Pharmaceutical compositions and methods of use of inhibitors of [alpha] 4 [beta] 7 integrin are disclosed. In particular, methods of using the [alpha] 4 [beta] 7 inhibitors in the treatment of diseases or conditions associated with inflammatory bowel diseases, including ulcerative colitis and Crohn's disease.

In some embodiments, the invention provides a method for identifying an agent beneficial to treat a patient with inflammatory bowel disease comprising: a) determining a status of an intestinal barrier in the patient; and b) categorizing the status as severe dysfunction or moderate dysfunction, wherein a patient categorized as having severe dysfunction is identified as a patient who will benefit from treatment with an agent selected from the group consisting of an anti-TNF agent and / or an anti-IL-12 / 23 agent, and a patient categorized as having moderate dysfunction is identified as a patient who will benefit from treatment with an anti-integrin agent, an anti-janus kinase agent, and / or and a sphingosine-1-phosphate receptor agonist agent.

The application provides a combined drug, a liposome, a biomimetic liposome, a preparation method of the combined drug, the liposome and the biomimetic liposome, and application of the combined drug, the liposome and the biomimetic liposome in preparation of an anti-breast cancer lung metastasis drug, and belongs to the technical field of biological medicines. The combined drug comprises panatinib and ginsenoside Rg3. The application further provides a liposome PNT-Rg3-Lipo for simultaneously loading the two, and a biomimetic liposome MM / PNT-Rg3-Lipo coated with a macrophage membrane. Experiments show that the combination of the two can synergistically regulate chemokines CXCL1 , CXCL2 and CXCL11 , and the effect is better than the sum of the single use. The MM / PNT-Rg3-Lipo has uniform particle size, retains integrin alpha 4 / beta 1 functional proteins, can target lung metastases, significantly reduces metastatic nodules, and has good biocompatibility. The application provides an effective new strategy for resisting breast cancer lung metastasis.

Provided herein are variant α4β7 integrin antibodies and methods of use.

Provided are alpha V beta6 and alpha V beta 1 integrin inhibitors, methods of making such alpha V beta6 and alpha V beta 1 integrin inhibitors, pharmaceutical compositions of alpha V beta6 and alpha V beta 1 integrin inhibitors and methods of treating and / or preventing various medical disorders in subjects in need of treatment by administration of alpha V beta6 and alpha V beta 1 integrin inhibitors.

Provided herein are variant α4β7 integrin antibodies and methods of use.

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Described herein are methods of improving atrial function and reducing atrial arrhythmias in a subject in need thereof. In one embodiment, the method comprises administering to the subject a therapeutically effective amount of a cardiac bridging integrator 1 (cBIN1) gene therapy. In some aspects, the subject exhibits one or more improved atrial properties following administration of the cBIN1 gene therapy relative to before administration of the cBIN1 gene therapy. These improved atrial properties may comprise shortened P-wave duration, reduced atrial fibrosis, reduced left atrial dyssynchrony, increased intracellular T-tubule area, reduced atrial arrhythmia, or combinations thereof.

The invention relates to the technical field of medicines, in particular to application of an integrin beta3 inhibitor RGDfK in preparation of a medicine for treating metabolic dysfunction related fatty liver diseases. The RGDfK provided by the invention can inhibit palmitoylation and membrane localization of CD36 in liver tissues of mice with fatty liver diseases related to metabolic dysfunction induced by high fat diet feeding, so that lipid uptake of the liver is inhibited. Experimental results show that RGDfK can improve obesity and insulin resistance of mice with metabolic dysfunction-related fatty liver diseases, can improve fat accumulation, fibrosis and inflammatory infiltration of liver tissues of the mice with fatty liver diseases, and is expected to become a new medicine for treating the metabolic dysfunction-related fatty liver diseases.

Methods for inhibiting or preventing activation of a macrophage, by a receptor antagonist of α9β1 integrin are provided. Further provided are methods for treating or preventing an inflammatory disease or a metabolic disorder, including a metabolic syndrome, in a subject in need thereof, and a pharmaceutical composition comprising a peptide comprising the amino acid sequence: EDDMMEVPY, for use in treatment or prevention of an inflammatory disease or a disorder, in a subject in need thereof.

Provided herein are integrin inhibitors, compositions thereof, and methods of their uses. Crystalline forms of salts of the inhibitors are also described, along with methods of preparing the crystalline forms. X-ray powder diffraction data, thermogravimetric analysis, and differential scanning calorimetry data are provided for the crystalline forms. The integrin inhibitors are useful for treatment of, inter alia, fibrotic diseases.

The disclosure relates to fixed dose combinations of the integrin inhibitor bexotegrast ((S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-l,8-naphthyridin-2-yl)butyl)amino)-2- (quinazolin-4-ylamino)butanoic acid) with peroxisome proliferator-activated receptor agonists (PPAR agonists), and methods of treating a subject for a liver fibrotic disease, such as primary sclerosing cholangitis or primary biliary cholangitis, by administration of the fixed dose combinations.

The invention belongs to the technical field of biological medicine, and particularly relates to an engineered cell exosome for specifically targeting liver, construction and application. The exosome is derived from mesenchymal stromal cells of an overexpressed integrin subunit beta 5, and the mesenchymal stromal cells of the overexpressed integrin subunit beta 5 are prepared by lentivirus infection. The liver targeting engineered umbilical cord mesenchymal stromal cell exosome can be remarkably enriched in liver tissue after intravenous infusion, the in-vivo anti-fibrosis curative effect is improved, the cell source of the engineered exosome is easy to obtain, the problem of exosome yield is solved, and good application prospects are shown.

The invention discloses a pharmaceutical composition and application of the pharmaceutical composition in preparation of medicines for treating bladder cancer or colorectal cancer. The pharmaceutical composition comprises at least one of an integrin alpha5beta1 inhibitor, an immune checkpoint inhibitor combination and a biocompatible hydrogel. The pharmaceutical composition can form a hydrogel microenvironment at the local part of a tumor in a local administration mode, continuously release effective components, cooperatively inhibit angiogenesis, improve an immunosuppressive microenvironment and reduce dry-like tumor cells, so that the immunotherapy effect is remarkably enhanced, and the toxic and side effects of the whole body are reduced. Single cell transcriptomics verification and animal experiments prove the feasibility of the pharmaceutical composition in inhibiting angiogenesis and tumor dryness and improving ICI curative effect.

Blocking antibodies against αMβ2 (CBP-α-αMβ2), αM (CBP-α-αM), α3 (CBP-α-α3), and anti-TGFβ as well as inhibitors of Talin2 reverse fibrosis in a mouse fibrosis model. Accordingly, aspects of the disclosure relate to inhibitors of Talin2 and inhibitors of the integrins αMβ2, αM, and α3. Aspects relate to a method for treating and / or reversing fibrosis in a subject comprising administering a composition comprising an inhibitor of Talin2 or a composition comprising a nucleic acid of the disclosure. Further aspects relate to a method for treating and / or reversing fibrosis in a subject comprising administering a composition comprising an antibody conjugate of the disclosure or a composition comprising an inhibitor or blocking agent of integrin α3, αM, αMβ2, or combinations thereof to the subject. Methods also include treating kidney fibrosis in a subject comprising administering a composition comprising an anti-TGFβ antibody operatively linked to an ECM-affinity peptide. The methods may be for reducing or decreasing the amount of existing fibrosis. The methods differ from traditional methods for treating fibrosis, since the current methods do not delay or inhibit the progression of fibrosis, but instead have shown to reverse, reduce, and / or decrease existing fibrosis. Accordingly, methods of the disclosure may be used in a manner that provides treatment to existing fibrosis rather than a prophylactic to prevent more fibrosis.

Provided herein are variant α4β7 integrin antibodies and methods of use.

To provide a method for treating disease.SOLUTION: The present disclosure provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula (I), processes for preparing compounds of Formula (I), and therapeutic methods for treating inflammatory disease. The present disclosure relates generally to novel compounds that have α4β7 integrin inhibitory action, prodrugs of compounds having α4β7 integrin inhibitory action, and methods of use and manufacture thereof.SELECTED DRAWING: None

The present invention addresses the problem of providing technology that is for preventing or treating the progression of liver conditions leading to liver cancer and targets a phenomenon other than hepatocyte death. This problem is solved by a prophylactic or therapeutic agent that is for at least one disease selected from the group consisting of liver fibrosis, cirrhosis, and liver cancer, contains at least one substance selected from the group consisting of CTGF inhibitors and integrin αV inhibitors, and is for patients suspected of having increased intrasinusoidal pressure.

The present disclosure relates to compounds of Formula (A) and Formula (I), for example: (I) or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, L1, L2, L3, Y, and Q are as described herein. Compounds of formula (A) and formula (I) and pharmaceutical compositions thereof are inhibitors of at least one or more of avPs, avPi and avPe integrin. Also disclosed are methods of treating fibrosis, such as non-alcoholic steatohepatitis (NASH), idiopathic pulmonary fibrosis (IPF), and non-specific interstitial pneumonia (NSIP), as well as cancer, comprising administering the compounds and pharmaceutical compositions thereof.

Anti-alpha4beta7 integrin antibody liquid formulations are described that have a high concentration of antibody, e.g., 90 mg / ml or more, have a viscosity suitable for injection for subcutaneous delivery, including by self-administration by the patient. In certain embodiments, formulations can be used in combination with an autoinjector having a suitable force of delivery given the viscosity of the formulation.

The present invention relates to compounds that are α4β7 integrin inhibitors. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with α4β7.

The disclosure relates to methods of reversing or retarding progression of fibrosis in a subject (such as a human) in need thereof, and methods of reversing or retarding collagen deposition in a subject (such as a human) in need thereof, comprising administering to the subject a therapeutically effective amount of (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2-(quinazolin-4-ylamino)butanoic acid, or a pharmaceutically acceptable salt thereof. In certain embodiments, the subject has a lung fibrotic disease, such as idiopathic pulmonary fibrosis, or a liver fibrotic disease such as primary sclerosing cholangitis. Methods of determining changes in collagen deposition in a subject following administration of a dual αvβ1 / αvβ6 integrin inhibitor, such as (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2-(quinazolin-4-ylamino)butanoic acid, or a pharmaceutically acceptable salt thereof, are also disclosed herein.

Linker-payload compounds comprise a JAK inhibitor and a cleavable linker, and antibody-drug conjugates (ADCs) comprise the same. ADCs targeting antigens associated with autoimmune or inflammatory diseases include but are not limited to integrin α4β7, MAdCAM-1, IL-17, IL-23, or TNF-α. The conjugates provided herein may comprise a variety of payloads, such as JAK inhibitors. Pharmaceutical compositions comprising the compounds or ADCs, and methods of producing them are also provided herein. Medical uses of these compounds and ADCs, including for the treatment of autoimmune diseases, inflammatory diseases, and fibrotic diseases, are also disclosed.

This invention relates to the field of biomimetic nanozymes and their preparation technology, disclosing a biomimetic nanozyme, its preparation method, and its applications. A peptide-functionalized biomimetic nanozyme (HRPL) is obtained by loading rapamycin onto HMPB nanozymes, coating the surface with a platelet membrane, and functionalizing it with the integrin-binding peptide LXW7. The binding of the platelet membrane to the LXW7 peptide enables targeted delivery to the site of endothelial injury, promoting endothelial repair and re-epithelialization. In an acidic inflammatory microenvironment, HRPL releases rapamycin, inhibiting smooth muscle cell proliferation and migration, and preventing restenosis. HRPL also scavenges reactive oxygen species, reducing oxidative stress and local inflammation, thereby improving the vascular microenvironment. The therapeutic effect was evaluated using a typical rat carotid balloon injury model. This dual-targeting mechanism not only promotes endothelial repair but also reduces restenosis and inflammation, showing significant clinical therapeutic potential. Especially after stent implantation, HRPL helps improve prognosis, reduce complications, and restore vascular homeostasis.

To provide a method for treating inflammatory bowel disease (IBD).SOLUTION: The present invention relates to methods of treating inflammatory bowel diseases, including with engineered peptides (e.g. peptide monomers and dimers comprising disulfide or thioether intramolecular bonds) that bind α4β7 integrin. In one aspect, the disclosure provides a method of treating an inflammatory bowel disease (IBD) in a subject in need thereof, comprising administering to the subject an α4β7 integrin antagonist, wherein the antagonist is administered to the patient orally at a dose of about 100 mg to about 500 mg, once or twice daily, wherein the antagonist is a peptide dimer compound comprising two peptides, or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: Figure 22

The present invention aims to provide an arthritis treatment agent containing synovial membrane-derived mesenchymal stem cells having molecules essential for joint treatment, and a method for producing the arthritis treatment agent. [Solution] According to the present invention, an arthritis treatment agent is provided which comprises synovial mesenchymal stem cells having one or more surface antigens, either integrin β1 or platelet-derived growth factor receptor β.

Described herein are compositions and methods for treating, preventing, reducing the likelihood of having, reducing the severity of and / or slowing the progression of a medical condition related to diabetic cardiomyopathy in a subject using cardiac bridging integrator 1 (cBIN1) as a therapeutic agent. In one embodiment, the compositions and methods comprise a cBIN1 gene therapy. In another embodiment, the disclosed compositions and methods may reduce blood glucose levels in a subject.

The present invention relates to a pharmaceutical composition to be used in the prevention or treatment of diseases involving vascular fibrosis. Specifically, the pharmaceutical composition according to the present invention contains a peptide that reduces fibrosis of perivascular tissue or the extracellular matrix constituting the vascular wall, and is useful for preventing or treating diseases involving vascular fibrosis, particularly pulmonary arterial hypertension.

The invention belongs to the technical field of cosmetics, and particularly relates to cyclic peptide for promoting expression of human skin full-configuration protein and application of the cyclic peptide in cosmetics. The structure of the cyclic peptide is shown as a formula (I) or (II). The cyclopeptide provided by the invention can significantly up-regulate the expression levels of COL1A1, COL3A1, ELN and ITGB1 in human dermal fibroblasts and promote the synthesis of collagen, elastin and integrin, so that the skin elasticity and compactness can be improved, and the cyclopeptide has excellent stability and biological safety. The cyclic peptide disclosed by the invention can be widely applied to cosmetics for resisting aging, improving skin elasticity, tightening and repairing. (I) (II)