45 results about "Complement factor B" patented technology

Provided are a compound as shown in general formula (I), or a stereoisomer, deuterate, solvate, prodrug, metabolite, pharmaceutically acceptable salt or co-crystal thereof, an intermediate thereof, a preparation method therefor, and the use thereof in the preparation of a drug for treating a disease associated with the activity or expression quantity of complement factor B.

The present invention belongs to the field of biotechnology. Disclosed is a dosage composition of a complement factor B inhibitor. Specifically, the present invention provides a pharmaceutical composition comprising a compound represented by formula I, an isomer thereof, or a pharmaceutically acceptable salt thereof in a unit dosage form, wherein the mass of the compound or the pharmaceutically acceptable salt thereof is 5-1500 mg based on the free base.

The present invention belongs to the technical field of biology. Disclosed are a crystal form of a complement factor B inhibitor, a preparation method therefor and the use thereof. Specifically, the present invention provides a crystal form of a compound represented by formula I, a preparation method therefor and the use thereof. The crystal form prepared by the present invention has good stability, for example, crystal form stability and thermal stability.

Aspects of the disclosure provide compounds, compositions, and methods for modulating the expression or activity of Complement Factor B (CFB). In certain aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of CFB mRNA in a cell or animal. In certain aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of CFB protein in a cell or animal.

The invention discloses application of CFB polypeptide as a target spot in preparation of diabetic nephropathy diagnosis and treatment medicines, and belongs to the technical field of biological medicines. The invention provides application of CFB (circulating fluid bed)-sourced polypeptide in preparation of a medicine for treating diabetic nephropathy and application of the CFB-sourced polypeptide as a possible target in development of a novel diabetic nephropathy biomarker. According to the invention, a complement factor B-derived polypeptide which is significantly up-regulated in diabetic nephropathy is found through deep peptidomics analysis; furthermore, a functional experiment proves that the polypeptide shows remarkable anti-fibrosis activity in kidney cells for the first time, the active oxygen level can be reduced, and an HIF-1 alpha / glycolytic pathway can be regulated and controlled.

The present invention relates to the technical field of biology. Disclosed are a salt of a complement factor B inhibitor, a preparation method therefor and a use thereof. Specifically, the present invention provides a salt of a compound as shown in formula (A), a preparation method therefor and a use thereof.

Relates to the technical field of nucleic acid drugs, and particularly provides a double-stranded oligonucleotide for inhibiting complement factor B (CFB) gene expression, the double-stranded oligonucleotide comprises a sense strand and an antisense strand, the positive-sense strand comprises at least 15 continuous nucleotides in any sequence as shown in SEQ ID NO: 1-SEQ ID NO: 255 in a table 1 or a nucleotide sequence which is different from the at least 15 continuous nucleotides by not more than 3 nucleotides; and / or the antisense strand comprises at least 15 contiguous nucleotides in any sequence as shown in SEQ ID NO: 256-SEQ ID NO: 510 in the table 1 or a nucleotide sequence which is different from the at least 15 contiguous nucleotides by not more than 3 nucleotides. The double-stranded oligonucleotide can inhibit CFB gene expression in cells and achieve the effects of relieving, treating and / or preventing diseases or symptoms mediated by CFB gene expression abnormity.

This disclosure relates to RNAi agents capable of inhibiting complement factor B (CFB) gene expression. Pharmaceutical compositions containing CFB RNAi agents and methods of use thereof are also disclosed. The CFB RNAi agents disclosed herein may be conjugated to a targeted ligand containing an N-acetyl-galactosamine ligand to facilitate in vivo delivery to hepatocytes. RNAi agents can be used in methods of treating diseases, disorders, or conditions partially mediated by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membrane proliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), anti-glomerular basement membrane antibody disease (anti-GBM), ischemia-reperfusion injury and T-cell-mediated rejection in kidney transplantation (TCMR), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD) including early and / or intermediate-stage AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated disorders.

The present invention provides compositions and methods that can be used to reduce CFB gene expression and to treat CFB-related diseases and conditions. It also provides CFB dsRNA agents, CFB antisense polynucleotide agents, compositions containing CFB dsRNA agents, and compositions containing CFB antisense polynucleotide agents that can be used to reduce CFB expression in cells and subjects.

Compositions and methods useful for reducing CFB gene expression and for treating CFB-related diseases and disorders are provided. Provided are CFB dsRNA agents, CFB antisense polynucleotide agents, compositions comprising CFB dsRNA agents, and compositions comprising CFB antisense polynucleotide agents that can be used to reduce CFB expression in cells and subjects.

A pharmaceutically acceptable salt type and crystal form of a compound of formula (I), and a preparation method of the compound and an application thereof are provided.

The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with dysregulation of the complement alternative pathway by administering a Complement Factor B (CFB) specific inhibitor to a subject.

Provided herein are methods of ameliorating a disease or disorder associated with dysregulation of the alternative complement pathway by administering a Complement Factor B (CFB) specific inhibitor to a subject.

The invention relates to a polysubstituted indole compound as well as a preparation method and application thereof. Specifically, the invention discloses a compound as shown in a formula (I), or a pharmaceutically acceptable salt thereof, or a prodrug thereof, the compound is a complement factor B inhibitor, has a significant inhibitory effect on complement factor B, and is high in bioavailability and excellent in pharmacokinetics.

The invention discloses siRNA (small interfering Ribonucleic Acid) for inhibiting CFB (circulating fluid bed) gene expression and application of the siRNA. The siRNA and the nucleic acid conjugate provided by the invention can effectively prevent and / or treat complement factor B mediated related diseases.

The invention provides a small interfering RNA (Ribonucleic Acid) for inhibiting expression of a complement factor B (CFB) and application of the small interfering RNA to preparation of a medicine for treating diseases related to expression of the complement factor B.

Disclosed in the present invention are a piperidine-substituted benzoic acid compound, and a pharmaceutical composition and the use thereof. The piperidine-substituted benzoic acid compound of the present invention is a compound as shown in formula (I) or a stereoisomer, a tautomer or an isotopic label thereof, or a pharmaceutically acceptable salt of any one of the foregoing. The compound has a good inhibitory activity on complement factor B, a good affinity activity on complement factor B, and a hemolytic activity and an inhibitory activity of an alternative complement pathway.

Provided is use of a complement factor B inhibitor in the preparation of a drug for treating or preventing IgA nephropathy or a disease or condition related thereto. Specifically, provided is use of a compound represented by formula I or a pharmaceutically acceptable salt thereof or a hydrate thereof in the preparation of a drug for treating or preventing IgA nephropathy or a disease or condition related thereto. The drug can effectively reduce creatinine and urea nitrogen levels in patients with IgA nephropathy, reduce renal inflammation and / or fibrosis in patients with IgA nephropathy, and provide a novel, effective and safe option for the treatment of IgA nephropathy.

The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and / or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated diseases.

The present application relates to an RNA inhibitor for inhibiting gene expression of a complement factor B (CFB) in a cell, comprising an antisense strand. The antisense strand and at least 15 consecutive nucleotides in an mRNA (SEQ ID NO: 8) encoding a CFB form a target sequence complementary region, the target sequence complementary region has 0, 1, 2, 3, 4 or 5 mismatches, and preferably, the complementary region has a length of 15-30 nucleotide pairs, and more preferably 17-23 nucleotide pairs.

Nucleic acid products that modulate, in particular interfere with or inhibit CFB gene expression, are provided. The products may be oligomeric compounds that comprise at least a first region of linked nucleosides having at least a first nucleobase sequence that is at least partially complementary to at least a portion o 5 f RNA transcribed from a CFB gene, where the first nucleobase sequence is selected from SEQ ID NOs 1 to 391, 751 and 752, or a fragment thereof.

Compositions and methods useful to reduce expression of CFB gene and for treatment of CFB-associated diseases and conditions are provided. Provided are CFB dsRNA agents, CFB antisense polynucleotide agents, compositions comprising CFB dsRNA agents, and compositions comprising CFB antisense polynucleotide agents that can be used to reduce CFB expression in cells and subjects.

The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and / or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated diseases.

Aspects of the disclosure provide compounds, compositions, and methods for modulating the expression or activity of Complement Factor B (CFB). In certain aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of CFB mRNA in a. cell or animal. In certain aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of CFB protein in a cell or animal.

The present invention relates to complement factor B inhibitors of formula (I), pharmaceutical compositions thereof and uses thereof. [Formula 1] TIFF2026502231000352.tif47167

Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof useful for treating diseases or disorders mediated by the complement factor B. (I)

Provided herein are substituted indole compounds. In certain embodiments, the compounds are inhibitors of the alternative pathway of the complement system, and in particular, inhibitors of complement factor B (CFB). Also provided are compositions comprising the compounds and methods of use thereof. The compounds provided are useful in the treatment, prevention or amelioration of a disease, condition or disorder through inhibition of the complement alternative pathway.

The present application provides a piperidinyl indole derivative, a preparation method and application thereof, in particular, the present application provides a compound with structural formula A and I or a pharmaceutically acceptable form thereof, which can be used for preparing a drug for treating a disease or disorder mediated by a disorder of a complement bypass pathway, in particular, a drug for treating a disease or disorder mediated by complement factor B.

Compositions and methods useful to reduce expression of CFB gene and for treatment of CFB-associated diseases and conditions are provided. Provided are CFB dsRNA agents, CFB antisense polynucleotide agents, compositions comprising CFB dsRNA agents, and compositions comprising CFB antisense polynucleotide agents that can be used to reduce CFB expression in cells and subjects.

The present application relates to a complement factor B inhibitor of formula (I), a pharmaceutical composition thereof, and the use thereof.