32 results about "Autosomal dominant polycystic kidney disease" patented technology

Novobiocin analogues are useful in methods of treating, inhibiting, and / or preventing cyst formation in autosomal dominant polycystic kidney disease (ADPKD) in a subject. The disclosure provides methods of treating ADPKD comprising administering a therapeutically effective amount of a coumarin-3-carboxamide novobiocin analogue. Accordingly, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of mTOR pathway phosphoproteins P-mTOR, P-Akt and P-S6K, or combinations thereof. Further, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of Hsp-90 client proteins CFTR, ErbB2, c-Raf and Cdk4, or combinations thereof.

The invention discloses application of ginkgolide B to preparation of medicament for preventing and / or treating autosomal dominant polycystic kidney disease. A madin-darby canine kidney (MDCK) vesicle model is used for screening to find that the ginkgolide B inhibits formation and growth of vesicles. An experimental result shows that: the ginkgolide B has an obvious inhibiting effect on the formation and growth of MDCK vesicles and the effect of the ginkgolide B is in dose response relationship; the ginkgolide B has no cytotoxicity to MDCK cells, so that the vesicle inhibiting effect of the ginkgolide B is independent of the cytotoxicity; the ginkgolide B does not obviously induce MDCK cell apoptosis, so that the vesicle inhibiting effect of the ginkgolide B is independent of cell apoptosis promotion of the ginkgolide B; the ginkgolide B can promote the MDCK cells or vesicles to form tubular structures; and the effect is in dose response relationship; and the ginkgolide B has an inhibiting effect on the growth of the embryonic kidney vesicles. The ginkgolide B provides experimental data for development of a specific medicament for preventing and / or treating autosomal dominant polycystic kidney disease.

The invention discloses application of curcumin to preparation of medicaments for preventing and / or treating autosomal dominant polycystic kidney disease. A madin-darby canine kidney (MDCK) vesicle model is used for screening to obtain the curcumin which inhibits formation and growth of vesicles. An experimental result shows that: the curcumin has an obvious inhibiting effect on the formation and growth of MDCK vesicles and the effect of the curcumin is in dose response relationship; the curcumin has no cytotoxicity to MDCK cells, so that the vesicle inhibiting effect of the curcumin is independent of the cytotoxicity; the curcumin does not obviously induce MDCK cell apoptosis, so that the vesicle inhibiting effect of the curcumin is independent of cell apoptosis promotion of the curcumin; the curcumin can promote the MDCK cells or vesicles to form tubular structures; and the effect is in dose response relationship; and the curcumin has an inhibiting effect on the growth of the embryonic kidney vesicles. The curcumin is expected to be developed into a specific medicament for preventing and / or treating autosomal dominant polycystic kidney disease.

The invention relates to the technical field of medicine, in particular to application of EZH2 (enhancer of zeste homolog 2) in the preparation of drugs to prevent or treat polycystic kidney disease.It is discovered herein that an EZH2 inhibitor can inhibit the proliferation of cyst cells by inducing the apoptosis of polycystic kidney disease cyst lining epithelial cells and regulating cell cycle, and can protect the renal function by inhibiting the growth of renal cysts and enlargement of renal size. It is indicated that EZH2 can act as a novel target for autosomal dominant polycystic kidneydisease and is very significant to the treatment of polycystic kidney disease; the EZH2 inhibitor can be used to develop new pilot compounds to prevent or treat autosomal dominant polycystic kidney disease and can also be used to prepare drugs to prevent or treat autosomal dominant polycystic kidney disease.

The invention provides application of fingolimod (2-amino-2-[2-(4-octylphenyl) ethyl]-1,3-propanediol) or salts thereof in preparation of medicinal compositions for treating cystic diseases. Particularly, the inventor finds that fingolimod or salts thereof have the effects of inducing the apoptosis and / or inhibiting the proliferation of a cystic cell by inhibiting HDACs and arresting the cell cycle of the cystic cell at G2 / M so as to reduce the cystic volume and restore the renal function. In addition, cytotoxicity experiments also confirm that during the treatment of the cystic diseases, fingolimod, as a known marketed medicine, has no obvious toxicity under the therapeutic dose. Fingolimod, as a medicine for treating the cystic diseases, especially an autosomal dominant polycystic kidney disease, has a wide application prospect.

The present invention relates to medicine molecular biology engineering technology, and is one kind of 1N-end fusion protein PC-1-e2 of human polycystic protein-1. According to cDNA sequence of human polycystic kidney disease-1 gene and the molecular structure of its encoded product, polycystic protein-1 (PC-1), the gene is cloned to cDNA-PKD1e2 in the N end of the protein and its prokaryotic expression carrier pQE30-PKD1e2 is constituted by means of molecular biology engineering technology. N-end fusion protein PC-1-e2 of PC-1 is induced in colibacillus. Cytobiology experiment shows that the fusion protein has obvious inhibition to the proliferation of the epidermis cell line of in vitro cultured human polycystic kidney cyst lining and the epidermis cell strain of far end renal tubule in dog kidney, so that it may be used in preparing medicine for treating autosomal dominant hereditary polycystic kidney disease, the reagent for the mechanism research of the disease, and anti-PC-1 antibody.

This invention provides a method of comparing disease markers obtained from subject samples to test for, detect, or diagnose autosomal dominant polycystic kidney disease and a disease marker for such disease. The method for detecting autosomal dominant polycystic kidney disease and the method for screening for an agent for treatment or prevention of such disease comprise detecting a gene that is expressed specifically in cases of autosomal dominant polycystic kidney disease, including IGFBP7.

A new type of kidney miniature organoids based on human embryonic stem cells are prepared and tested as forming cysts in vitro or ex vivo. Assays are developed for screening useful candidate molecules towards inhibiting or treating polycystic kidney disease. This provides a new system for modeling polycystic kidney disease.

Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

Provided herein are methods for the treatment of poly-cystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

Provided herein are methods for the treatment of poly-cystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

The invention belongs to a technology of medical in vitro diagnosis, and in particular relates to an amplification primer for detecting mutation of autosomal dominant polycystic kidney disease-causing gene PKD2 as well as a detection method. The amplification primer, in accordance with the sequence information of the PKD2 gene, designs four pairs of PCR primers; the PKD2 is subjected to targeted amplification by virtue of long-chain PCR; and an amplification region includes all exon sequences and most intron sequences, as well as partial 5' untranslated region sequences and 3' untranslated region sequences. According to the method, by combining long-chain PCR targeted amplification to the newest developed next generation of sequencing technology, a targeted sequencing process is simplified, the scope and flux of detecting the PKD2 gene mutation are improved, a detection cycle is shortened and cost is reduced.

The invention discloses STR sites of a PKD2 gene. The STR sites are selected from nucleotide sequences as show in SEQ ID NO.1-SEQ ID NO.6. The invention also discloses an application of the STR sites of the PKD2 gene, wherein the STR sites are applicable to preimplantation genetic diagnosis or prenatal disgnosis of autosomal dominant polycystic kidney disease. The STR sites of the PKD2 gene are higher in resolution ratio; and the STR sites, when applied to linkage genetic analysis of the PKD2 gene, can significantly improve typing recognition efficiency and accuracy; therefore, a basis is provided for the clinical preimplantation genetic diagnosis of the autosomal dominant polycystic kidney disease.

The disclosure provides a use of C3aR in preparing drugs for preventing or treating polycystic kidney disease, belonging to the technical field of medicines. The disclosure discovers that C3aR inhibitor can down-regulate or reduce the C3aR level by inhibiting proliferation of cyst epithelial cells, blocking chemotaxis of C3a-C3aR on macrophages, inhibiting the interaction between C3a and C3aR, and expressing the p-ERK, p-P65 proteins, and then prevent cyst growth, improve the inflammatory state, thus treating polycystic kidney disease. The C3aR inhibitor can be used for the development of novel lead compounds for preventing or treating autosomal dominant polycystic kidney disease, and also can be used for preparing drugs for preventing or treating polycystic kidney disease.

The process for the diagnosis, early detection and prognosis of the clinical development of autosomal-dominant polycystic kidney disease (ADPKD) comprises the step of determining the presence or absence or amplitude of at least three polypeptide markers in a urine sample, the polypeptide markers being selected from the markers characterized in Table 1 by values for the molecular masses and migration times.

The invention provides an application of cyclodextrin in preparation of a medicine for treating and / or preventing polycystic kidney disease, and belongs to the technical field of biology. According tothe invention, an ADPKD model is applied to prove that after hydroxypropyl-beta-cyclodextrin removes a fossa structure on the surface of a polycystic kidney cyst tissue cell membrane, the expressionof caveolin-1 (CAV1) is reduced, so that the purpose of treating and / or preventing autosomal dominant polycystic kidney disease caused by gene mutation is achieved.

The invention discloses an aminoalcohol compound, its preparation method, a pharmaceutical composition containing the compound and an application of the compound. The structure of the compound is as shown in the general formula (I), wherein A, R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined in the specification and the claims. The compound provided by the invention can be used in the preparation of drugs for preventing and / or treating autosomal dominant polycystic kidney disease.

A method for diagnosing a predisposition for accelerated autosomal dominant polycystic kidney disease (ADPKD) in a human male subject by detecting the Glu 298 Asp polymorphism of the ENOS gene is described. A diagnostic kit for detecting predisposition for accelerated ADPKD in a human subject is also disclosed. In addition, a method for treating a human subject predisposed to develop accelerated APDKD using NO-enhancing compounds is provided.

Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

The invention relates to the application of pyrimidine (thio) ketone compounds in the preparation of medicines for treating secretory diarrhea and autosomal dominant hereditary polycystic kidney disease. Cystic fibrosis transmembrane conductance regulator is a Cl-channel protein activated by cyclic adenosine monophosphate. During the design of the model, multiple activation pathways of CFTR were considered, and multiple activation pathways were combined to screen During the process, it binds at the Cl-transport channel. The application of pyrimidine (thio) ketone compounds in the preparation of drugs for treating secretory diarrhea and autosomal dominant polycystic kidney disease is screened on the basis of screening a large number of compounds by using the model for screening inhibitors directly combined with CFTR. It can effectively prevent and treat the occurrence of swine diarrhea. Effectively inhibits fluid secretion from epithelial cells lining autosomal dominant polycystic kidney cysts. The inhibitory effect is rapid, and there is no obvious toxic effect.

The invention discloses STR sites of a PKD2 gene. The STR sites are selected from nucleotide sequences as show in SEQ ID NO.1-SEQ ID NO.6. The invention also discloses an application of the STR sites of the PKD2 gene, wherein the STR sites are applicable to preimplantation genetic diagnosis or prenatal disgnosis of autosomal dominant polycystic kidney disease. The STR sites of the PKD2 gene are higher in resolution ratio; and the STR sites, when applied to linkage genetic analysis of the PKD2 gene, can significantly improve typing recognition efficiency and accuracy; therefore, a basis is provided for the clinical preimplantation genetic diagnosis of the autosomal dominant polycystic kidney disease.

The invention provides the application of 1-indanone in the preparation of medicine for treating or preventing autosomal dominant polycystic kidney disease. The present invention uses the MDCK vesicle model to prove that 1-indanone can inhibit the formation and growth of vesicles, and determines the renal pharmacological activity of 1-indanone through the in vitro embryonic kidney vesicle model, which has a significant effect on the development of vesicles in the kidney. Finally, it was further proved in the polycystic kidney mouse model that 1-indanone also had the effect of inhibiting the occurrence and development of vesicles in vivo. The above-mentioned vesicle inhibitory effects in vitro and in vivo showed a dose-effect relationship.

The invention proves, through the application of an MDCK (Madin-Darby canine kidney cells) vesicular model, that an FAK (focal adhesion kinase) inhibitor can inhibit the generation and growth of vesicles, can determine intrarenal pharmacological activity of the FAK inhibitor through an in-vitro embryonal vesicular model, and can inhibit the progress of intrarenal vesicles significantly. The invention further proves finally, in a polycystic renal mouse model, that the FAK inhibitor can also inhibit the progress of vesicles in vivo, while the in-vitro and in-vivo vesicular inhibitory actions arein dose-effect relationship. The FAK inhibitor never affects the activity of renal cells; it is indicated that the ability of the FAK inhibitor to polycystic kidney is irrelevant to its cytotoxicity,and that the FAK inhibitor can regulate intracellular signal pathways, which may be one of its important mechanisms to inhibit the progress of renal vesicles. The FAK inhibitor is VS4718 which is suitable for treating autosomal dominant polycystic kidney disease.