109 results about "Farnesoid X receptor" patented technology

The invention relates to the discovery that farnesoid X receptor (FXR) agonists can be used in combination with peroxisome proliferation activated receptor gamma (PPARγ) agonists to reduce drug-induced adverse side effects in patients suffering from conditions such as insulin resistance, Type II diabetes, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and heart disease. Particularly, the present invention encompasses methods for treating patients suffering from drug-induced adverse side effects with selective PPARγ, dual PPARα/γ and pan PPARα/γ/δ agonists in combination with FXR agonists.

The present invention relates to a method for inhibiting fibrosis that occurs in an organ where the farnesoid X receptor (FXR) is expressed. This method involves the step of administering a high potency, activating ligand of FXR in an effective amount to a patient who is not suffering from a cholestatic condition. The invention also provides pharmaceutical compositions containing an effective amount of an FXR ligand and kits for dispensing the pharmaceutical compositions.

The invention relates to a compound shown as formula (I), a pharmaceutically acceptable salt, ester or stereoisomer thereof. R1, R2, R3, R4, m, n, W, A, Z, E, F, X and Y are defined as the specification. The invention also relates to a preparation method of the compounds, pharmaceutical preparations and application in drugs for treatment and/or prevention of FXR (farnesoid X receptor) mediated nonalcoholic fatty liver diseases, primary biliary cirrhosis, lipid metabolism disorders, diabetic complications, malignant tumors and other related diseases. (formula (I)).

The invention relates to a compound shown as formula (I), a pharmaceutically acceptable salt, ester or stereoisomer thereof. R1, R2, R3, R4, m, n, W, A, Z, E, F, X and Y are defined as the specification. The invention also relates to a preparation method of the compounds, pharmaceutical preparations and application in drugs for treatment and/or prevention of FXR (farnesoid X receptor) mediated nonalcoholic fatty liver diseases, primary biliary cirrhosis, lipid metabolism disorders, diabetic complications, malignant tumors and other related diseases. (formula (I)).

The present invention relates to famesoid X receptors (FXR, NR1 H4) FXR is a member of the nuclear receptor class of ligand-activated transcription factors. More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceutical formulations comprising such compounds, and therapeutic use of the same Novel isoxazole compounds are disclosed as part of pharmaceutical compositions for the treatment of a condition mediated by decreased FXR activity, such as obesity, diabetes, cholestatic liver disease and metabolic syndrome.

Disorders of the skin and mucous membranes that have a disrupted or dysfunctional epidermal barrier are treated or prevented by topical application of compounds that are either activators of the farnesoid X receptor, activators of the peroxisome proliferator-activated receptor alpha , and oxysterol activators of the LXR alpha receptor. The same compounds are also effective in treating disorders of epidermal differentiation and proliferation.

A preventive and/or therapeutic agent for diabetes, comprising a substance capable of inhibiting the activity of farnesoid X receptor as an active ingredient.

The present invention relates to compounds of Formula I, a stereoisomer, enantiomer, a pharmaceutically acceptable salt or an amino acid conjugate thereof; wherein variables are as defined herein; and their pharmaceutical compositions, which are useful as modulators of the activity of Farnesoid X receptors (FXR).

The invention belongs to the technical field of medicines, and particularly relates to a compound as shown in the formula (I), and pharmaceutically acceptable salt and ester or a stereisomer thereof.R1, R2, R3, M1, M2, m, n, Q, L, ring A, ring B and ring C are as defined in the specification. The invention further relates to a preparation method of the compounds, and application in preparing medicines for treating and/or preventing related diseases such as non-alcoholic fatty liver disease, primary biliary cirrhosis, lipid metabolism disorders, diabetic complication and malignant tumors mediated by an FXR. The formula (I) is shown in the description.

Compounds, compositions and methods are provided for treating the FXR-mediated disease or process in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound claimed, wherein the FXR-mediated disease or condition linked to chronic liver diseases such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis; gastrointestinal diseases; cardiovascular diseases; metabolic diseases such as diabetes and obesity; inflammation, or cancer etc.

The present invention relates to the field of biomedicine. The present invention provides application of a farnesoid X receptor (FXR) expression interference reagent in preparation of anti-hepatic fibrosis drugs. Specifically, the present invention relates to application of FXR for treatment of hepatic fibrosis, by tail intravenous injection of the farnesoid X receptor (FXR) expression interference reagent (namely, an adenovirus carrying FXR plasmid) to mice, the expression level of the FXR in hepatocytes is significantly increased, CCl4-induced hepatic fibrosis can be significantly countered,hepatocyte morphology and structural integrity can be maintained, and serum transaminase level can be reduced. A new approach for clinical treatment of liver diseases especially hepatic fibrosis is provided.

Methods of identifying agents effective as inhibitors of short heterodimer protein (SHP) and farnesoid X receptor (FXR) and promoters, cell lines and vectors used in said methods. Methods of preparing and using the agents effective as inhibitors of short heterodimer protein (SHP), including methods of using same to prevent and/or treat a condition associated with inflammatory gene activity and/or cholesterol biosynthesis in a subject. Agents effective as inhibitors of short heterodimer protein (SHP) and farnesoid X receptor (FXR) and compositions comprising same, including compositions effective in reducing inflammatory gene activity and/or cholesterol biosynthesis in a subject.

The invention relates to preparation of carboxylic acid derivatives and application of the carboxylic acid derivatives serving as an FXR (farnesoid X receptor) antagonist and particularly provides a compound shown as a formula (I), or a pharmaceutically acceptable salt of the compound and a preparation method of the compound. In the formula (I) as shown in the specification, R1 is selected from hydrogen, methyl, methoxyl, halogen, nitryl and carboxyl; X is selected from NH or O; n1 is 0 or 1; n2 is 0 or 1; R1 and a radical as shown in the specification are positioned at any substitution positions of a benzene ring. The compound shown as the formula (I) or the pharmaceutically acceptable salt thereof has a pharmacological effect of blood fat reduction and can be used as the FXR antagonist.

The invention belongs to the technical field of medicines, and particularly relates to a compound as shown in the formula (I), and pharmaceutically acceptable salt and ester or a stereisomer thereof.R1, R2, R3, R4, W, A, Z, E, X, Y and n are as defined in the specification and the claims. The invention further relates to a preparation method of the compounds, pharmaceutical preparation and application in preparing medicines for treating and/or preventing related diseases such as non-alcoholic fatty liver disease, primary biliary cirrhosis, lipid metabolism disorders, diabetic complication andmalignant tumors mediated by an FXR. The formula (I) is shown in the description.

The invention provides methods for modulating the activity of farnesoid X receptors (FXRs) using specific FXR agonists, in particular for treating or preventing liver and gastrointestinal diseases.

The invention relates to the field of natural medicines, and in particular relates to an action mechanism of silybin for preventing liver apoptosis through an FXR (Farnesoid X Receptor) path. According to the invention, the silybin prevents apoptosis of HepG2 cells caused by ActD/TNF alpha through an FXR dependent path. Within human hepatoma cell line HepG2 cells, silybin can induce up-regulation of mRNA level and protein level of FXR in a dose-dependent manner, and can reverse down-regulation of FXR expression in a HepG2 cell apoptosis model caused by ActD/TNFalpha remarkably; the silybin has remarkable protective effect on the HepG2 cell apoptosis caused by the ActD/TNFalpha, but the anti-apoptosis function of the silybin is lost after the FXR SiRNA is used for silencing endogenous FXR genes.

The invention belongs to the field of biomedicines, and relates to application of a nuclear FXR (Farnesoid X Receptor) in targeted therapy of liver cancer stem cells. The nuclear FXR is used as a target for diagnosing or assisting in diagnosis of the liver cancer stem cells, and a gene medicine or a chemical medicine is designed to be applied to treatment of the liver cancer stem cells. According to the application of the nuclear FXR in the targeted therapy of the liver cancer stem cells, the gene medicine is an FXR-containing expression vector or interference vector; the chemical medicine contains a ligand for regulating the FXR and a ligand for regulating a target gene of the FXR. According to the application, by virtue of cell transfection and activation of the nuclear FXR, the tumor ball formation capacity of a hepatoma cell line can be obviously reduced, and the tumorigenicity of the liver cancer stem cells is reduced; a new molecular target is supplied to identification of the liver cancer stem cells and diagnosis and treatment of the liver cancer, so that the problem that a conventional molecular marker of tumor stem cells is hard to regulate is solved.

The invention is concerned with novel benzimidazole derivatives of formula (I)

wherein R¹ to R⁸ are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds bind to Farnesoid-X-receptors (FXR) and can be used to treat diseases which are modulated by FXR agonists such as diabetes and dyslipidemia.

According to the present invention, an agent for prophylactic and/or therapeutic treatment of diabetes comprising a substance inhibiting activity of farnesoid X receptor as an active ingredient can be provided.

According to the invention, a farnesoid X receptor (FXR) antagonist is applied to treatment of HBV infected persons. Serum bile acid in the HBV infected persons can promote HBV replication and expression through the FXR, and the FXR receptor antagonist can inhibit the HBV replication and expression, promote HBV cleaning, improve hepatic functions, inhibit hepatic fibrosis and hepatic cirrhosis and reduce risk of metastasis of liver cancer.

The invention provides methods for modulating the activity of farnesoid X receptors (FXRs) using specific FXR agonists, in particular for treating or preventing liver diseases and disorders.