30 results about "PPAR agonist" patented technology

The invention discloses a method for promoting skeletal muscle development and application, and belongs to the technical field of biology. The invention provides a method for promoting skeletal muscle development, an AMPK / p38MAPK pathway is regulated and controlled by activating PPARalpha, the way of activating the PPARalpha is to give a PPARalpha agonist GW7647, and the regulation and control of the AMPK / p38MAPK pathway is shown as reduction of AMPK and P38 phosphorylation levels. Experiments show that the expression of MyoD, MyoG and Pax7 in skeletal muscle can be remarkably improved by activating PPARalpha, the phosphorylation level of AMPK and P38 is inhibited, and therefore muscle fiber proliferation and myoblast proliferation are promoted. The technology can be applied to livestock breeding to improve meat yield or develop drugs for treating skeletal muscle atrophy, and has remarkable economic and clinical values.

A method of treating nephrotic syndrome (NS) in a subject is described. The method includes administering a therapeutically effective amount of a PPARγ agonist to the subject.

Provided are methods of treating subjects in need of an anti-fibroblast growth factor receptor 4 (anti-FGFR4) therapy. The methods comprise administering to the subjects a therapeutically effective amount of a peroxisome proliferator-activated receptor (PPAR) alpha agonist in combination with the anti-FGFR4 therapy. The methods can comprise administering to the subject a therapeutically effective amount of PPAR alpha agonist and a bile acid sequestrant. Also provided are compositions comprising an FGFR4 inhibitor, a PPAR alpha agonist, and, optionally, a bile acid sequestrant. The methods attenuate the dysregulation of bile acid biosynthesis caused by FGFR4 inhibition with anti-FGFR4 therapies. The methods reduce the severity and / or incidence of adverse events associated with anti-FGFR4 therapies.

This invention provides an application of tartary buckwheat antioxidant peptide as a PPARα agonist. The tartary buckwheat antioxidant peptide (SEQ ID NO:1) is used to prepare a PPARα agonist, and this tartary buckwheat antioxidant peptide is used to prepare a drug for improving metabolic dysfunction-related fatty liver disease (MASLD). The tartary buckwheat antioxidant peptide of this invention provides a new drug candidate for improving MASLD and has broad clinical application prospects.

The invention provides an application method of a PPAR gamma agonist in preparation of a medicine for inhibiting ferroptosis of nucleus pulposus cells, and belongs to the technical field of medicine preparation.The PPAR gamma agonist pioglitazone and TAT cell-penetrating peptide are combined to form a compound, the compound is encapsulated in hyaluronic acid modified pH-sensitive lipidosome to construct a nucleus pulposus targeted drug delivery system, and the nucleus pulposus targeted drug delivery system is used for inhibiting ferroptosis of the nucleus pulposus cells. The flow cytometry is utilized to detect the physicochemical properties of the drug delivery system, the optimal drug delivery parameters are determined through a double-layer game optimization model, the drug release kinetics is determined in different pH environments to establish a pH response release model, and finally the PPAR gamma and Axl protein expression levels and the GPX4 protein level are detected through the fluorescence luminescence to verify the ferroptosis resisting effect. The technical problem that a drug carrier system cannot realize dual-function collaborative optimization of targeted delivery and acid-sensitive controlled release of nucleus pulposus cells is solved.

Prenylated tetrahydroquinolines and quinolines and pharmaceutical compositions comprising the same. Prenylated tetrahydroquinoline and quinolines and pharmaceutical compositions comprising the same, for use in the prevention and / or treatment of peroxisome proliferator-activated receptor (PPAR)-mediated diseases such as metabolic syndrome, type 2 diabetes mellitus, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, dyslipidemic atherosclerosis, metabolic dysfunction- associated fatty liver disease (MAFLD), cardiovascular disease, cardiometabolic disease, neurodegenerative disease, Friedreich's ataxia, Parkinson's disease, multiple sclerosis, Alzheimer's disease, autoimmune disease, rheumatoid arthritis, autoimmune thyroid disease, dermatological disease, and cancer.

The present invention provides compounds as PPAR agonists and their application, involving a new class of peroxisome proliferator-activated receptor (PPAR) gamma receptor agonist, which can inhibit the production of mitochondrial reactive oxygen species, and most of which can readily cross the blood-brain barrier. The present invention also includes pharmaceutical uses of the compounds.

This invention provides a mitochondrial-targeting compound—triphenylphosphine GW7647 conjugate (TPP-GW)—that can effectively enhance anti-tumor function, a pharmaceutical composition containing TPP-GW, and a method for preparing and using the TPP-GW. The triphenylphosphine GW7647 conjugate is obtained by conjugating (3-aminopropyl)triphenylphosphine with GW7647. It is a novel mitochondrial-targeting PPARα agonist that can enhance the toxic effects of the original GW7647 on tumor cells and has a synergistic effect with immune checkpoint blockade therapy.

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.

Microparticulate (MP) formulations formed from one or more poly(hydroxyacid) polymers having a molecular weight ranging from 5kD to 60kD, and one or more active agents are injected into the eye of a subject to address eye disorders. The MP formulations assure high drug loading and extended delivery of the active agent of six to twelve months. The active agents may include peroxisome proliferator-activated receptor alpha (PPARα) signaling agonists such as PPARα agonist A190 (IUPAC name 3-((4-((4-fluorobenzyl)oxy)- 3- methylbenzyl)amino)benzoic acid). The formulations have therapeutic and protective effects against retinal degeneration diseases such as age-related macular degeneration (AMD), but may also be used for treating or relieving the symptoms of retinal inflammation, retinal neovascularization, retinal vascular leakage, retinopathy of prematurity (ROP), diabetic retinopathy (DR), and diabetic macular edema (DME).

This specification provides a method for reducing or reversing age-induced insulin resistance and / or fatty acid elevation, comprising a composition comprising a PPAR agonist, or a pharmaceutically acceptable salt or prodrug thereof. This specification also provides a method for extending lifespan, comprising a composition comprising a PPAR agonist, or a pharmaceutically acceptable salt or prodrug thereof, and its use in animal health.

The pharmaceutical compound or the pharmaceutically acceptable salt thereof is used for preventing or treating the following diseases by simultaneously inhibiting autotaxin (ATX) and activating peroxisome proliferator-activated receptor gamma (PPAR gamma): a) fibroproliferative diseases, in particular interstitial lung diseases (ILD) and / or liver diseases, and b) fibroproliferative diseases, in particular interstitial lung diseases (ILD) and / or liver diseases; the present invention relates to a pharmaceutical composition for treating hepatitis, such as various hepatitis and / or non-alcoholic fatty liver disease (NAFLD) and / or non-alcoholic steatohepatitis (NASH) and / or cirrhosis, where said ILD may be a primary disease, preferably idiopathic pulmonary fibrosis and / or sarcoidosis and / or interstitial pneumonia, or said ILD is a complication associated with an autoimmune and / or inflammatory and / or metabolic disease, or a pharmaceutical composition comprising said ILD. Preferably rheumatoid arthritis ILD and / or scleroderma ILD and / or myositis ILD and / or diabetes ILD and / or cardiovascular disease ILD; and / or b) inflammatory and / or autoimmune diseases, preferably rheumatoid arthritis and / or scleroderma; and / or c) cancer, in particular lung and / or hepatocellular carcinoma and / or pancreatic cancer and / or glioblastoma and / or neuroblastoma; and / or d) a metabolic disease, in particular diabetes mellitus type 1 and / or diabetes mellitus type 2 and / or obesity, having a formula selected from the group consisting of formulae (A), (B), (C), (D), (E), (F), (G) and (H).

The present application belongs to the technical field of biological medicine, and particularly relates to a composition for promoting synthesis of an OAHFA derivative family, a microneedle patch and application thereof in preventing and treating dry eye syndrome. The present application first selects an OAHFA derivative as a dry eye treatment target and relies on activation of a PPARγ signal pathway to exert drug efficacy. The composition is compounded from 0.2% to 0.5% PPARγ agonists, 2.0% to 4.0% super-long chain fatty acids and 0.3% to 0.8% ceramides, three effective components. The super-long chain fatty acids supply synthesis substrates, and the ceramides stabilize the interface. The three components synergistically improve the curative effect. The composition described in the present application adopts soluble microneedles for local administration, and the drug release rate is not less than 70% in 30 min. The effect is rapid and the puncture is painless, and the patient compliance is excellent. Local administration eliminates systemic exposure of the drug, and the drug safety is high, and there is no serious adverse reaction.

The present invention provides a pharmaceutical composition for use in preventing or treating metabolic diseases comprising a novel pan-PPAR agonist compound or a salt thereof as an active ingredient. As the pan-PPAR agonist, the compound or the salt thereof may be useful in pharmaceutical compositions for preventing or treating metabolic diseases such as obesity, diabetes, fatty liver diseases, dyslipidemia, cardiovascular diseases, and / or metabolic syndrome, and in food or feed compositions for improving metabolic health.

Provided are methods of treating subjects in need of an anti-fibroblast growth factor receptor 3 (anti-FGFR3) therapy. The methods comprise administering to the subjects a therapeutically effective amount of a peroxisome proliferator-activated receptor (PPAR) alpha agonist in combination with the anti-FGFR3 therapy. The methods can comprise administering to the subject a therapeutically effective amount of PPAR alpha agonist and a bile acid sequestrant. Also provided are compositions comprising an FGFR3 inhibitor, a PPAR alpha agonist, and, optionally, a bile acid sequestrant. The methods attenuate the dysregulation of bile acid biosynthesis caused by FGFR3 inhibition with anti-FGFR3 therapies. The methods reduce the severity and / or incidence of adverse events associated with anti-FGFR3 therapies.

The present application belongs to the field of pharmaceutical technology, and specifically relates to compounds and their preparation methods, as well as their use in the preparation of sEH inhibitors and PPAR agonists. The present application provides compounds having the structures shown in Formula I, II, III, IV, V, or VI. The compounds provided herein have a typical urea structure as the primary pharmacophore for soluble epoxide hydrolase (sEH) and a thiazolidinedione moiety as the primary pharmacophore for peroxisome proliferator-activated receptors (PPARs). The sEH inhibitor and PPAR agonist compounds provided herein have high inhibitory activity against human HsEH and high agonistic activity against PPARs, and can be used as sEH inhibitor and PPAR agonist compounds for the preparation of drugs for the treatment of soluble epoxidase- and peroxisome proliferator-activated receptor-mediated diseases.

The present invention relates to a combination therapy comprising a PPAR agonist, such as elafibranor, and a GLP-1 receptor agonist, such as semaglutide, liraglutide, exenatide, lixisenatide, albiglutide and dulaglutide, for the treatment of a condition is selected from the group consisting of non-alcoholic fatty liver disease, diabetes and obesity.

The present invention relates to a pharmaceutical compound or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of the following conditions, wherein the pharmaceutical compound or a pharmaceutically acceptable salt thereof is characterized in that it simultaneously inhibits autotaxin (ATX) and agonizes PPARγ, and has a chemical formula selected from the group consisting of formulas (A), (B), (C), (D), (E), (F), (G), and (H): a) fibroproliferative diseases, in particular interstitial lung diseases (ILD) and / or liver diseases such as all types of hepatitis and / or non-alcoholic fatty liver disease (NAFLD) and / or non-alcoholic steatohepatitis (NASH) and / or cirrhosis, where the ILD is a primary disease, preferably idiopathic pulmonary fibrosis and / or sarcoidosis and / or interstitial pneumonia, or where the ILD is associated with an autoimmune and / or inflammatory and / or metabolic disease, preferably rheumatoid arthritis-ILD ​​and / or scleroderma-ILD and / or myositis-ILD ​​and / or diabetes-ILD ​​and / or cardiovascular disease-ILD combination, and / or b) an inflammatory and / or autoimmune disease, preferably rheumatoid arthritis and / or scleroderma, and / or c) cancer, in particular lung cancer and / or hepatocellular carcinoma and / or pancreatic cancer and / or glioblastoma and / or neuroblastoma, and / or d) metabolic diseases, in particular type 1 diabetes and / or type 2 diabetes and / or obesity [Formula 1] TIFF2026503883000014.tif94126

Compositions and topical formulations comprising a PPAR agonist complex comprising glyceryl linoleate, glyceryl linolenate, xymenynic acid, and Pterocarpus marsupium bark extract are described herein. Methods of inducing skin barrier repair, increasing the biosynthesis of barrier lipids and proteins in the skin, stimulating hair growth, treating acne and combinations thereof utilizing the composition and topical formulations are also provided herein.

Dendrimer-drug compositions have been developed that not only target the reactive inflammatory cells / macrophages in the plaque, but also in the adipose tissue, delivering drugs in a targeted manner to simultaneously and independently address both atherosclerosis and obesity, and associated metabolic disorders.   The dendrimers are preferably glucose dendrimers, hydroxyl-terminated PAMAM dendrimers, or sugar-modified dendrimers, most preferably glucose dendrimers.   The drugs are preferably a PPAR-α agonist; a PPAR-γ agonist; a dual PPAR agonist (e.g., a PPAR- α / γ agonists); a GLP-1 receptor agonist (e.g., semaglutide); a metformin; an SGLT2 agonist, a GIP-1 receptor agonist or antagonist; a dual GLP-1 / GIP-1 receptor agonist (e.g., tirzepatide); a mitochondrial uncoupler (e.g., niclosamide); or a combination thereof. These compositions have the ability to overcome the side effects of current drugs for obesity and heart disease, and open new avenues in addressing these disorders through targeting of selective cells.

This invention belongs to the field of pharmaceutical technology, specifically relating to a compound, its preparation method, and its application in the preparation of sEH inhibitors and PPARs agonists. This invention provides a compound having the structure shown in Formula II. The compound provided by this invention has a typical urea structure as the primary pharmacophore of soluble epoxide hydrolase (sEH), and a thiazolidinedione moiety as the primary pharmacophore of peroxisome proliferator-activated receptors (PPARs). The sEH inhibitor and PPARs agonist compound provided by this invention exhibits high inhibitory activity against human HsEH and high agonistic activity against PPARs, and can be used as an sEH inhibitor and PPARs agonist compound in the preparation of drugs for treating diseases mediated by soluble epoxide hydrolase and peroxisome proliferator-activated receptors.

The invention provides a combined use of a dihydroquinoline derivative and a PPARalpha agonist, and particularly relates to an application of a specific dihydroquinoline derivative and a PPARalpha agonist in preparation of a product for preventing or treating fatty liver. It is found for the first time that the combination of the specific dihydroquinoline derivative and the PPARalpha agonist can significantly reduce the triglyceride level of the liver, so that alcohol-induced liver fatty degeneration is relieved, and the application has good clinical transformation prospects.

The present application relates to the technical field of medicines, and in particular to a compound, and a preparation method therefor and a use thereof in the preparation of a soluble epoxide hydrolase (sEH) inhibitor and a peroxisome proliferators-activated receptors (PPARs) agonist. The present application provides a compound, having a structure represented by formula I, II, III, IV, V or VI. The compound provided by the present application has a typical urea structure as the primary pharmacophore of an sEH, and the thiazolidinedione part serves as the primary pharmacophore of PPARs. The sEH inhibitor and PPARs agonist compound provided by the present application has high inhibitory activity against human-derived HsEH and high agonistic activity against a PPAR, and can be used for the preparation of a drug for treating soluble epoxide enzyme and PPARs-mediated diseases.

The application belongs to the technical field of medicine, and particularly relates to a compound, a preparation method thereof and application of the compound in preparation of sEH inhibitors and PPARs agonists. The application provides a compound with a structure shown in formula V or VI. The compound provided by the application has a typical urea structure as a primary pharmacophore of soluble epoxide hydrolase (sEH) and a thiazolidinedione part as a primary pharmacophore of peroxisome proliferator-activated receptors (PPARs). The sEH inhibitor and PPARs agonist compound provided by the application has high inhibitory activity on human HsEH and high agonistic activity on PPARs, and can be used as an sEH inhibitor and PPARs agonist compound for preparation of a medicine for treating diseases mediated by soluble epoxide hydrolase and peroxisome proliferator-activated receptors.

The invention relates to the technical field of biological medicines, and provides application of a PPARalpha (peroxisome proliferator activated receptor alpha) agonist, namely fenofibrate Feyfibrate, Wy14643 and PEA (peroxisome proliferator activated receptor alpha). The PPARalpha agonists Fenofirate, Wy14643 and PEA provided by the invention can be directly or indirectly combined with PPARalpha protein through specificity and activate the activity of the PPARalpha protein, so that a PPARalpha signal channel is regulated, and diarrhea reaction after stimulation of new coronavirus is relieved. The Fenofibrate, the Wy14643 and the PEA disclosed by the invention are high in treatment specificity, small in side effect and good in effect when being used for treating new coronavirus infection.

Methods for treating a disease, condition, or disorder associated with impaired muscle regeneration, including a muscular dystrophy, such as Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), or limb-girdle muscular dystrophy (LGMD), by administering a PPARγ agonist to a subject. The PPARγ agonist can be one or more thiazolidinediones including, but not limited to pioglitazone and rosiglitazone.

A method of treating or preventing glomerular disease or chronic kidney disease in a subject is described. The method includes administering to the subject a therapeutically effective amount of PPARγ agonist or a pharmaceutically acceptable salt thereof.

The present invention relates to the use of sodium glucose transporter 2 (SGLT2) inhibitors for the prevention or delay of clinical complications of blood disorders, preferably anaemia or clinical complications of anaemia, in patients who having been treated, treated or planned to be treated with a PPAR agonist.