24 results about "Focal segmental glomerulosclerosis" patented technology

The disclosure provides at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt chosen from compounds of Formula I, tautomers thereof, deuterated derivatives of those compounds or tautomers, and pharmaceutically acceptable salts of any of the foregoing, compositions comprising the same, and methods of using the same, including uses in treating APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and / or non-diabetic kidney disease (NDKD).

The disclosure provides at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt chosen from compounds of Formula I, tautomers thereof, deuterated derivatives of those compounds or tautomers, and pharmaceutically acceptable salts of any of the foregoing, compositions comprising the same, and methods of using the same, including uses in treating APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and / or non-diabetic kidney disease (NDKD).

The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here the inventors show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions. Accordingly, CD9 represents a reliable biomarker and as well as a biotargets in glomerulonephritides.

Described herein are fusion proteins which include factor H functional domains and may include VHH domains and integrin binding domains, and the use of such fusion proteins in methods of treatment of focal segmental glomerulosclerosis.

Methods for treating primary glomerulonephritis, e.g., focal segmental glomerulosclerosis (FSGS), IgA nephropathy (IgAN) or mesangial proliferative glomerulonephritis (MsPGN) are provided.

Provided herein are methods of treating focal segmental glomerulosclerosis (FSGS), comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to a subject in need thereof. Also provided herein are methods of decreasing renal inflammation and / or fibrosis, reducing the rate of decline in eGFR, delaying the onset of ESKD, decreasing proteinuria, and decreasing fatigue in a subject having FSGS, comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to the subject.

The application discloses a chemical structural formula of a biphenyl sulfonamide compound of a bis-benzimidazole, and also discloses application of the compound in preparation of a pharmaceutically acceptable salt or solvate, application of the compound and the pharmaceutically acceptable salt or solvate in preparation of a medicine for treating endothelin-dependent or angiotensin II-dependent diseases. Meanwhile, the biphenyl sulfonamide compound of the bis-benzimidazole can also be used in combination by changing substituted functional groups. The biphenyl sulfonamide compound of the bis-benzimidazole, the prepared pharmaceutically acceptable salt or solvate and the medicine prepared by the compound have pharmacological activities, and have pharmacological effects in animals including human beings, and are particularly useful in treatment or prevention of IgA nephropathy, focal segmental glomerulosclerosis, nephrotic syndrome, chronic kidney disease, diabetic nephropathy, hypertension, coronary heart disease and myocardial infarction.

The present disclosure provides at least one entity selected from a compound of Formula I, a tautomer thereof, a deuterated derivative of the compound or tautomer, and a pharmaceutically acceptable salt of any of the foregoing, compositions comprising the entity, and methods of use thereof, including use in the treatment of APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and / or non-diabetic kidney disease (NDKD).

The invention discloses application of an SHIP1 agonist AQX-1125 in preparation of a medicine for treating focal segmental glomerulosclerosis, and belongs to the technical field of medicines.The endogenous regulatory factor SHIP1 agonist is used for conducting precise speed limiting on a PI3K / Akt pathway, so that a new effective means is provided for FSGS treatment, and the application form of the SHIP1 agonist AQX-1125 can be an oral preparation and the like; tests prove that the AQX-1125 can remarkably repair renal functions, reduce pathological proteinuria, improve pathological damage of kidney tissues, maintain phenotypic homeostasis and ultrastructural integrity of podocyte and accurately regulate and control pathogenic signal pathways and metabolic homeostasis, so that the AQX-1125 shows remarkable technical progress and clinical application potential in the aspect of FSGS treatment.

Disclosed are methods for treating focal segmental glomerulosclerosis (FSGS) comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula (I) wherein R1 to R7, A, L, and Y are as defined herein. Also disclosed are pharmaceutical compositions comprising the compounds of formula (I) and their use for the treatment of FSGS.

The disclosure provides at least one entity chosen from compounds of Formula I, a tautomer thereof, a deuterated derivative of that compound or tautomer, and a pharmaceutically acceptable salt of any of the foregoing, compositions comprising the same, and methods of using the same, including uses in treating APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and / or non-diabetic kidney disease (NDKD).

The invention relates to a biomarker for evaluating focal segmental glomerulosclerosis and application thereof, and relates to the technical field of detection. The biomarker comprises the cloning quantity of the urine-derived stem cells and / or the CLDN1 genes of the urine-derived stem cells. On the basis of the biomarker, urine-derived stem cell characteristics of FSGS and healthy people and other kidney diseases can be effectively distinguished by using a non-invasive means, and the biomarker is used for detecting the cell molecular level and is applied to diagnosis, evaluation and monitoring of FSGS.

The invention discloses application of integrin alpha3 as a focal segmental glomerulosclerosis biomarker, and belongs to the technical field of biological detection. A sample used for detection is kidney tissue, and the expression level and distribution of integrin alpha3 in the sample are detected. By detecting and analyzing the expression level and distribution of the integrin alpha 3 in the epithelial cells of the cyst wall layer in the glomerulus, the segmental sclerosis globules in the early stage of the disease can be identified, and the method is an effective method for assisting in diagnosing focal segmental glomerulosclerosis.

The disclosure provides at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt chosen from compounds of Formula I, tautomers thereof, deuterated derivatives of those compounds or tautomers, and pharmaceutically acceptable salts of any of the foregoing, compositions comprising the same, and methods of using the same, including uses in treating APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and / or non-diabetic kidney disease (NDKD).

The disclosure provides at least one compound, tautomer, deuterated derivative, or pharmaceutically acceptable salt chosen from compounds of Formula I, tautomers thereof, deuterated derivatives of those compounds or tautomers, and pharmaceutically acceptable salts of any of the foregoing, compositions comprising the same, and methods of using the same, including uses in treating APOL1-mediated diseases, including pancreatic cancer, focal segmental glomerulosclerosis (FSGS), and / or non-diabetic kidney disease (NDKD).

Provided are oligonucleotides, polynucleotide conjugates, and compositions and populations comprising the same, as well as methods and uses thereof for reducing the amount or activity of Rho guanine nucleotide exchange factor 6 (ARHGEF6) RNA in a cell or animal, and in certain instances reducing the amount of ARHGEF6 protein in a cell or animal Such oligonucleotides, polynucleotide conjugates, and compositions and populations, methods and uses are useful to treat kidney diseases or conditions. In particular, such oligonucleotides, polynucleotide conjugates, and compositions and populations, methods and uses are useful to treat chronic kidney disease, such as diabetic nephropathy (DN), focal segmental glomerulosclerosis (FSGS), renal hypertension (HTN), IgA nephropathy / Berger's disease (IgAN), rapidly progressive glomerulonephritis (RPGN) and systemic lupus erythematosus (SLE).

The present invention relates to a novel salt of 2-amino-2-(2-(1-decyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol, and a pharmaceutical composition containing same. In the results of a comparison with hydrochloride salt of 2-amino-2-(2-(1-decyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol and the other salts thereof, the novel salt of 2-amino-2-(2-(1-decyl-1H-1,2,3-triazol-4-yl)ethyl)propane-1,3-diol, according to the present invention, exhibits excellent effects in all of low hygroscopicity, standard stock solution stability, photostability, oxidation stability, pH-dependent stability, solubility and the like. The pharmaceutical composition, of the present invention, containing the novel salt as an active ingredient, can be effectively used for preventing or treating multiple sclerosis, ischemic stroke, focal segmental glomerulosclerosis (FSGS), inflammatory bowel disease, interstitial fibrosis and tubular atrophy (IFTA) or alopecia areata (AA).

The present disclosure relates to ABCA1 inducer compounds for use in treating kidney disorders, and in particular, chronic kidney diseases, glomerular diseases or proteinuric kidney diseases such as Alport syndrome, focal segmental glomerulosclerosis, and diabetic kidney disease.

The invention belongs to the technical field of biological medicine, discloses application of WIF1 in preparation of a medicine for preventing and treating focal segmental glomerulosclerosis, and researches the relationship between the WIF1 and the occurrence and development of the focal segmental glomerulosclerosis by designing and constructing a mouse model in which a WIF1 gene is knocked out and a mouse model in which the WIF1 is overexpressed. Experimental results show that: knockout of the Wif1 gene can significantly aggravate damage of podocyte in focal segmental glomerulosclerosis and increase generation of proteinuria in focal segmental glomerulosclerosis; the overexpression of the Wif1 gene can significantly reduce the level of proteinuria in focal segmental glomerulosclerosis, significantly reduce the glomerular injury index in focal segmental glomerulosclerosis, and significantly improve podocyte injury. Therefore, the WIF1 has protection and improvement effects on the occurrence and development of the focal segmental glomerulosclerosis, and the WIF1 has a new application of preventing and treating the focal segmental glomerulosclerosis.

The invention discloses a kit for detecting specific early diagnosis of focal stage glomerulosclerosis, through innovative primer probe design and detection system optimization, the core advantage of the kit is that six miRNA markers, namely miR-125b, miR-186, miR-193a-3p, miR-17, miR-451 and miR-19b, which are verified by a multi-center queue are innovatively integrated; six groups of specific reverse transcription primers based on a stem-loop structure are successfully designed. According to the kit for specific early diagnosis of focal segmental glomerulosclerosis, aiming at the technical defects of low abundance, high sequence homology, poor multi-index detection compatibility and the like of focal segmental glomerulosclerosis (FSGS)-related miRNA, systematic optimization of a stem-loop reverse transcription method and a real-time fluorescent quantitative PCR (qPCR) two-step method is carried out, so that the specificity of the focal segmental glomerulosclerosis is improved, and the specificity of the focal segmental glomerulosclerosis is improved. The detection efficiency, the sensitivity and the specificity are obviously improved.

This application describes methods for inhibiting APOL1 and treating APOL1-mediated diseases, comprising administering Compound I and / or a pharmaceutically acceptable salt thereof. This application also describes pharmaceutical compositions comprising Compound I and / or a pharmaceutically acceptable salt thereof. JPEG2023515668000016.jpg5256

Provided herein are methods of treating focal segmental glomerulosclerosis (FSGS), comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to a subject in need thereof. Also provided herein are methods of decreasing renal inflammation and / or fibrosis, reducing the rate of decline in eGFR, delaying the onset of ESKD, decreasing proteinuria, and decreasing fatigue in a subject having FSGS, comprising administering a therapeutically effective amount of atrasentan, or a pharmaceutically acceptable salt thereof, to the subject.