36 results about "MTORC1" patented technology

The invention provides application of a small molecule drug for promoting triple negative breast cancer ferroptosis, and belongs to the technical field of tumor treatment. The inducer can effectively kill triple negative breast cancer cells by triggering a ferroptosis pathway. The invention discovers that the inhibitor can reduce the expression of a key protein RPTOR by inhibiting the activity of an mTORCl compound, thereby weakening the anti-oxidation defense capability of triple negative breast cancer cells, greatly enhancing the accumulation of lipid peroxide, and further strongly inducing the occurrence of ferroptosis. The component of the culture medium is a DMEM (Dulbecco Modified Eagle Medium) containing 10% of fetal calf serum, and 2 [mu] M of Torinl is added at the same time. The invention discloses a new target spot of ferroptosis of the triple-negative breast cancer, and provides a new thought for treatment of the triple-negative breast cancer.

The invention belongs to the technical field of biological medicine, discloses a novel venom polypeptide composite dendrimer as well as a preparation method and application thereof, and particularly discloses scorpion venom polypeptide, and the amino acid sequence of the scorpion venom polypeptide is FLGGSLSSIF. According to the invention, a novel scorpion venom polypeptide (marked as C9) is separated and identified, and a novel polypeptide-polyamidoamine dendritic compound G5C9 (i.e., nanoparticles) with a glioblastoma (GBM) targeting effect is constructed. Compared with the polypeptide C9, the cell uptake efficiency of the G5C9 is obviously improved. G5C9 can enter cells through endocytosis and target lysosome to destroy functions of the lysosome and mTORC1, so that nuclear translocation of TFEB is promoted, and autophagic death of the cells is induced. Therefore, the G5C9 provides a novel mode for targeting the anti-GBM in vitro and in vivo.

The disclosure provides methods for the acute treatment of depression and / or anxiety, for the enhancement of mTOR (e.g., mTORC1) signaling, and for the reduction of neuroinflammation, comprising administering to a patient in need thereof, a therapeutically effective amount of a 5-HT2A or 5-HT2A / D2 receptor ligand, e.g. lumateperone.

The present invention provides a cryoprotective additive for human sperm and a preparation method thereof. The method is to add an mTORC1 activator and a Caspase-9 inhibitor to a commercially available sperm cryoprotectant. Compared with the pure commercially available protectant, the cryoprotective additive of the present invention has an increased number of forward-moving sperm after thawing and recovery; there are more forward-moving sperm after recovery, with better forward motility and better forward motility endurance. At the same time, the mitochondrial structure and function of the sperm cells after recovery are less damaged, the mitochondrial function recovers quickly, less mitochondrial ROS is produced, apoptosis is reduced, the ability to protect the function of sperm cells is better, and it is more conducive to the long-term cryopreservation of sperm-like cells.

The disclosure provides methods for the acute treatment of depression and / or anxiety, for the enhancement of mTOR (e.g., mTORC1) signaling, and for the reduction of neuroinflammation, comprising administering to a patient in need thereof, a therapeutically effective amount of a 5-HT2A or 5-HT2A / D2 receptor ligand, e.g. lumateperone.

The present disclosure provides compounds and salts showing high selectivity and inhibitory activity against mTORC1 and their use in treating diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to an mTORC1 selective degradation agent containing a hydrophobic label as well as a synthesis method and application of the mTORC1 selective degradation agent. The structural formula of the degradation agent is as shown in formula I. Representative compounds have the effect of inhibiting proliferation of various tumor cells, and can provide new research and development thoughts and directions for anti-tumor drugs. .

The present specification relates to the use of an AKT inhibitor, a PI3K-alpha inhibitor or an mTOR (such as mTORC1) inhibitor in combination with a KDM5C inhibitor for the treatment of cancer, such as breast cancer. Also described is a pharmaceutical composition comprising a compound, a KDM5C inhibitor, and a pharmaceutically acceptable excipient wherein the compound is an AKT inhibitor, a PI3K-alpha inhibitor, or an mTOR inhibitor.

The disclosure provides methods for the acute treatment of depression and / or anxiety, for the enhancement of mTOR (e.g., mTORC1) signaling, and for the reduction of neuroinflammation, comprising administering to a patient in need thereof, a therapeutically effective amount of a 5-HT2A or 5-HT2A / D2 receptor ligand, e.g. lumateperone.

The present invention relates to compounds and methods useful for selectively modulating mTORC1 activity.The present invention describes compounds comprising a lithium salt and an mTORC1 activator in stoichiometric ratio or co-crystal form.Such mTORC1 activator can be an amino acid as described in published PCT application WO2017 / 070518.In some embodiments, the compounds comprising a lithium salt and an mTORC1 activator have improved efficacy due to the synergistic effect of lithium and mTORC1 activator.

The disclosure provides methods for the acute treatment of depression and / or anxiety, for the enhancement of mTOR (e.g., mTORC1) signaling, and for the reduction of neuroinflammation, comprising administering to a patient in need thereof, a therapeutically effective amount of a 5-HT2A or 5-HT2A / D2 receptor ligand, e.g. lumateperone.

A carcinostatic agent, a carcinogenesis inhibitor and / or a life-prolonging agent each comprising a compound with mTORC1 inhibitory effect, said compound having partial structures (I), (II) and (III), or a pharmacologically acceptable salt thereof. (In the formulae: R1, R2, R3 and R4 are the same or different and represent an H, a lower alkyl, a lower haloalkyl, a lower alkoxy, a lower alkylamino, an OH, a protected OH, an amino, a protected amino, a carboxy, a protected carboxy or a halogen atom; R5 and R6 are the same or different and represent an H or a protecting group of an OH, or R5 and R6 form together a methylene or dimethylmethylene group; and A represents O or S.)

The application belongs to the technical field of biological medicine, and provides application of astragaloside IV in preparation of a medicine for treating advanced ovarian cancer. The application analyzes and studies a targeting effect of AS-IV on CD276, determines a molecular mode of covalent combination of AS-IV and CD276, identifies a molecular mechanism of combination of AS-IV and CD276 through an E3 ubiquitin ligase and activation of an mTORC1 pathway of NK cells, and determines application potential of AS-IV in enhancement of NK cell anti-tumor immunity in preparation of an OC immunotherapy medicine.

The present invention includes compositions and methods for treating or preventing certain dermal disorders including dermal atrophy, pseudoscars, actinic keratosis, seborrheic or actinic keratoses, lentigines, focal areas of dermal thickening, and coarse wrinkles. In certain embodiments, the compositions useful within the invention comprise a therapeutically effective amount of a mTORC1 inhibitor and a dermatologically acceptable carrier.

The invention discloses a ZnPc-SFeCO compound as well as a preparation method and application thereof, and discloses a general drug design method taking [2Fe-2S] (CO) 6 as an active center, a drug design strategy based on an interference lysosome arginine-SLC38A9-mTORC1-CCDK2 / 4 / 6 path is established, ZnPc-SFeCO is taken as an example, the ZnPc-SFeCO efficiently catalyzes decomposition of arginine in lysosome so as to inhibit activation of SLC38A9, and the application of the ZnPc-SFeCO compound is promoted. According to the present invention, with the application of the CDK2 / 4 / 6, the collection and the activation of the mTORC1 can be accurately blocked, the CDK2 / 4 / 6 activation retardation cell cycle progress can be inhibited, and the treatment effect superior to the clinical first-line anticancer drug mitomycin (MMC) can be obtained in the in-vivo in-situ non-muscular invasive bladder cancer (NIMBC) model and the tumor recurrence prevention and lifetime prolonging experiment.

The invention belongs to the technical field of gene engineering, and particularly relates to a method for constructing a knock-down pig RagB gene cell strain. The invention aims to provide an experimental material for improving the utilization rate of amino acid by livestock and poultry. According to the technical scheme, the method for constructing the pig RagB gene knock-down cell strain comprises the following steps: designing shRNA (short hairpin Ribonucleic Acid) of a targeted RagB gene, constructing the shRNA on an expression vector, and transfecting IPEC-J2 cells; the nucleotide sequence of the shRNA is as shown in Seq ID (Identity) No. 6, Seq ID No. 7, Seq ID No. 9, Seq ID No. 10, Seq ID No. 12 or Seq ID No. 13. The invention successfully clones the porcine RagB gene and constructs the knock-down cell strain of the porcine RagB gene. The cell strain provides an experimental material for the subsequent research of the function of the RagB protein and the understanding of the effect of the RagB protein in mTORC1.

The invention belongs to the technical field of biology, and particularly relates to application of RAB3B in chordoma. The invention firstly provides an application of an RAB3B inhibitor in preparation of a product; the product is selected from: 1) a product for reducing the phosphorylation level of the S6 protein; (2) a product for regulating and controlling a PI3K-AKT-mTOR signal channel; and 3) a product for preventing and / or treating chordoma. The invention further provides application of the RAB3B and / or the reagent for detecting the RAB3B in preparation of a chordoma prognosis product or a product for predicting treatment response. By inhibiting RAB3B expression, proliferation of tumor cells of chordoma can be inhibited, the tumor volume of chordoma patients can be reduced, and by quantitatively detecting RAB3B expression in chordoma patient samples, the treatment response of the patients to the mTORC1 inhibitor and the prognosis condition of the patients to chordoma can be accurately predicted.

The application provides a tetrahedral framework nucleic acid carrying siRNA, a preparation method thereof and an application thereof in preparing anti-aging drugs, and belongs to the technical field of medicines.The siRNA for inhibiting the expression of rapamycin complex 1 (mTORC1) is carried on the tetrahedral framework nucleic acid to form a tetrahedral framework nucleic acid complex, the tetrahedral framework nucleic acid complex can exert a synergistic anti-aging effect, and the tetrahedral framework nucleic acid complex has a good application prospect in preparing anti-aging drugs.

To provide methods, compositions, and unit dosage forms useful for selectively modulating mTORC1 activity.SOLUTION: The present invention provides, inter alia, methods of treating depression comprising administering to a patient in need thereof a therapeutically effective amount of ((S)-2-amino-5,5-difluoro-4,4-dimethylpentanoic acid), or a pharmaceutically acceptable salt or composition thereof. In some embodiments, the depression is major depressive disorder (MDD). In some embodiments, the depression is treatment-resistant depression (TRD).SELECTED DRAWING: None

To provide compounds and methods useful for treating mTORC-mediated disorders.SOLUTION: The present invention provides novel rapamycin analogs that are potent mTORC1 inhibitors as measured by pS6K. Unlike rapamycin and everolimus, these compounds do not inhibit pAKT at relatively long time points (for example, 24 hours and 48 hours). These compounds also exhibit improved solubility and improved pharmacokinetics compared to rapamycin.SELECTED DRAWING: None

Methods for treating diseases or disorders associated with an increase in mTORC1 activity or inflammation, or elevated NT-proBNP, as well as methods of inducing autophagy in the treatment of diseases and disorders, with an ActRII ligand trap.

Provided are a new venom polypeptide-dendrimer complex, and a preparation method therefor and the use thereof. Specifically, provided is a scorpion venom polypeptide, wherein the amino acid sequence of the scorpion venom polypeptide is FLGGLLSSIF. A new scorpion venom polypeptide (designated as C9) is isolated and identified. Moreover, a new polypeptide-polyamidoamine dendrimer complex G5C9 (i.e., nanoparticles) having a glioblastoma (GBM)-targeting effect is constructed. Compared with polypeptide C9, G5C9 exhibits significantly improved cellular uptake efficiency. G5C9 can enter cells via endocytosis and targets lysosomes, and inhibits lysosomal function and mTORC1, thereby promoting nuclear translocation of TFEB and further inducing autophagic cell death. Therefore, G5C9 provides a new targeted anti-GBM approach both in vitro and in vivo.

The present disclosure provides MTORC1 modulators and uses thereof. In particular, the present disclosure provides compounds and salts that exhibit high selectivity and inhibitory activity for mTORC1 and their use for the treatment of disease.

The present disclosure relates to MTORC1 modulators and uses thereof. In particular, the present disclosure provides compounds and salts that exhibit high selectivity and inhibitory activity for mTORC1 and their use for the treatment of disease.