31 results about "PI3K signaling" patented technology

The present disclosure relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof and (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof. The present disclosure also relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof, (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof, and (3) a third agent which is an agent that regulates the PI3K / Akt / mTOR pathway or a pharmaceutically acceptable salt thereof.

This invention relates to the field of ovarian tissue in vitro culture technology, and discloses a formulation for activating and increasing follicles and its application. The formulation consists of a PI3K / Akt / mTOR pathway activator and / or a PTEN inhibitor SF1670. The PI3K / Akt / mTOR pathway activator is a 5-15 μM statin, and the PTEN inhibitor is a 20-50 μM SF1670. Using this formulation can achieve the follicle activation and increase effect of existing technologies, contributing to the development and selection of in vitro follicle activators in clinical practice. Furthermore, the use of this formulation opens up a new technological application area for statins.

The application provides an oxazinane compound, a preparation method, a pharmaceutical composition and application, and a general formula of the oxazinane compound or a pharmaceutically acceptable salt thereof is shown as formula (I). The oxazinane compound has obvious proliferation inhibition effect on cancer cells, especially human head and neck squamous cell carcinoma cell strains HSC4, HSC3, HSC2, CAL33, SCC4 and human glioma cell strain U251, can block the cell cycle, effectively inhibit the phosphorylation level of key proteins in the PI3K / AKT / mTOR pathway at the molecular level, has the potential to be prepared into a new antitumor drug, and has a good market prospect.

The present disclosure relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof and (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof. The present disclosure also relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof, (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof, and (3) a third agent which is an agent that regulates the PI3K / Akt / mTOR pathway or a pharmaceutically acceptable salt thereof.

The application provides a brain-targeting nano preparation loaded with ergosterol and a preparation method and application thereof, relates to the fields of nanometer materials and nanometer biological medicine, and the active ingredient ergosterol of the nano preparation is encapsulated in DSPE-PEG-pinacol boronate nanometer material, the nanometer material has ROS response characteristics, the nano preparation loaded with ergosterol is regular spherical, has uniform particle size, has good dispersibility and stability, has good ability of targeted treatment of ischemic stroke diseases, effectively solves the problems of poor targeting of ordinary drugs, low bioavailability and the like, enhances the treatment effect of ergosterol on ischemic stroke, can effectively improve brain damage caused by ischemic stroke, has good treatment effect, meanwhile, the active ingredient ergosterol plays a role in treating ischemic stroke by activating the PI3K / AKT / mTOR pathway, and provides a new direction for the treatment of ischemic stroke.

Compounds of the following formula:having defined substituents. The compounds can inhibit class II phosphoinositide 3-kinase (PI3K) signaling and are useful for the treatment of a medical condition associated with defective PI3K signaling, such as myopathy, cancer, diabetes, thrombosis or cardiovascular disease.

The invention relates to the technical field of biology, and discloses application of C646 in preparation of a primordial follicle in-vitro activator. The invention particularly relates to application of C646 in preparation of an mTOR agonist and / or an AKT signal channel key protein agonist. The C646 promotes the growth and differentiation of precursor granulosa cells into granulosa cells by improving the phosphorylation level of key protein on an mTOR / PI3K signal channel. In addition, C646 can also improve expression of AKT and further promote activation of primordial follicles, so that the number of primary follicles is increased. When the concentration of the C646 in the culture medium is 4 mu M, the primary follicles are obviously increased, which indicates that the 4 mu M C646 can obviously promote the activation of the original follicles. Meanwhile, in-vivo renal envelope transplantation experiments find that the ovary can stimulate activation of primordial follicles after being subjected to C646 short treatment.

To provide a method for treating diseases or disorders associated with PI3K signaling.SOLUTION: A method for inhibiting cell proliferation includes the steps of: bringing a cell in contact with an effective dose of a regulating substance of glucose metabolism; and bringing the cell in contact with an effective dose of at least one inhibitory substance of at least one kinase in an insulin receptor / PI3K / AKT / mTOR pathway, by which cell proliferation is inhibited.SELECTED DRAWING: Figure 10A

Described herein are compositions and methods for treating a disease or disorder associated with PI3K signaling. For example, such compositions can include use of modulators of glucose metabolism, use of at least one kinase in the insulin-receptor / PI3K / AKT / mTOR pathway, and / or use of diet that influences the subject's metabolic state.

The invention discloses a compound for targeted degradation of PI3K protein as well as a preparation method and application of the compound. The structural general formula of the compound is as shown in a formula I in the specification. Biochemical activity tests show that the compounds have a good inhibition effect on PI3K enzyme activity and can significantly degrade PI3K protein, so that the compounds can provide effective and better-selectivity degradation inhibitors for treatment of diseases regulated by PI3K, and are expected to be developed into drugs for treating diseases related to PI3K signal pathways, such as PI3K signal pathways, PI3K signal pathways, PI3K signal pathways, PI3K signal pathways, PI3K signal pathways, PI3K signal pathways and PI3K signal pathways. The target drugs can be used for treating gastric cancer, breast cancer, ovarian cancer, leukemia and the like. # imgabs0 #

The invention relates to the technical field of medicinal and edible compositions, in particular to a composition for relieving ovarian function decline based on cell autophagy and DNA methylation level. The composition for relieving ovarian function decline comprises 10-50 parts of collagen tripeptide, 1-5 parts of gamma-aminobutyric acid, 1-6 parts of a red grape yeast compound, 0.5-2 parts of a yeast extract, 1-6 parts of a sophora flower extract, 0.5-2 parts of golden camellia, 0.5-6 parts of a turmeric extract, 0.1-2.7 parts of blueberry anthocyanin, 1-8 parts of ginseng, 1-6 parts of an angelica sinensis extract, 1-6 parts of a poria cocos extract and 0.1-0.3 part of sodium hyaluronate. According to the composition disclosed by the invention, medicinal and edible substances are taken as main raw materials, and the raw material components are regulated and controlled, so that the composition can improve ovarian granular cell excessive autophagy, lower the methylation level and reduce ovarian granular cell damage on the basis of activating a PI3K / Akt / mTOR pathway, thereby relieving ovarian function decline.

The invention discloses application of carnosic acid in preparation of a medicine for treating traumatic ectopic ossification. The inventor finds that carnosic acid can reduce the overall level of ROS and inhibit a downstream PTEN / PI3K signal channel by researching the influence of carnosic acid on the intracellular ROS level and the downstream signal channel in the inflammation-induced tendon stem cell osteogenic differentiation process, so that the osteogenic differentiation of tendon stem cells is inhibited. Experimental results show that in an in-vivo experiment of burn and achilles tendon cutting ectopic ossification mice, the carnosic acid can relieve oxidative stress and osteogenic differentiation caused by trauma and inhibit ectopic ossification formation. Therefore, a new thought and a theoretical basis are provided for developing a new medicine for treating ectopic ossification, and the formation of traumatic ectopic ossification can be inhibited in a targeted manner by applying the carnosic acid.

The application provides a peptide lipid nanoparticle, a preparation method, an application and a cancer combined treatment drug combination, and belongs to the technical field of biological medicines.The application proposes a novel synergistic anti-tumor strategy based on the combination of a peptide lipid nanoparticle and a low-dose mTOR inhibitor, synergistically inhibits a PI3K / AKT / mTOR signal pathway, co-applies the peptide lipid nanoparticle loaded with p53 circular RNA and the mTOR inhibitor to cancer cells, restores p53 function, reactivates PTEN, blocks the feedback activation of PI3K / AKT, and directly inhibits mTOR by the mTOR inhibitor, thereby producing a persistent cascade double blocking. Moreover, p53 inhibits the evirolimus-induced pro-survival autophagy, converts it into a stress-induced process, and realizes the double inhibition and persistent blocking of the PI3K / AKT / mTOR pathway.

The invention provides an application of metformin in preparation of a medicine for preventing or treating immune checkpoint inhibitor related colitis. It is found through experiments that when the immune checkpoint inhibitor causes colitis, change of metabolic level represented by glycolysis caused by change of a PI3K / AKT / mTOR pathway in the colon is obviously accompanied, then Treg / Th17 steady state in the colon is affected, and a high inflammatory state is shown in the colon. According to the present invention, the influence on glycolysis and other metabolic pathways is achieved through the targeted interference of the metformin on the PI3K / AKT / mTOR pathway, the colitis caused by the immune checkpoint inhibitor can be significantly improved, the anti-tumor drug effect of the immune checkpoint inhibitor is not affected, and the method is generally superior to the original clinical methylprednisolone intervention scheme.

The invention discloses a series of compounds targeting PI3K protein and a preparation method and application thereof. The structural formula of the compounds is shown as a formula I or pharmaceutically acceptable salts of the compounds. Pharmacological activity tests show that the compound has a good inhibition effect on PI3K kinase activity, has good anti-proliferative activity on various tumor cells, and can significantly degrade PI3K protein. Therefore, the compounds can provide an effective degradation inhibitor for treatment of diseases regulated by PI3K, and are expected to be developed into targeted drugs for treating diseases related to PI3K signal pathways, such as gastric cancer, breast cancer, ovarian cancer, melanoma, colorectal cancer, leukemia and the like. # imgabs0 #

This invention discloses a pharmaceutical composition with preventive or therapeutic effects on liver injury. The pharmaceutical composition consists of turmeric dione and atractylodes lactone II. Through the synergistic effect of turmeric dione and atractylodes lactone II, it is used to treat liver injury caused by various reasons. Cell experiments show that this invention can effectively inhibit the proliferation activity of hepatic stellate cells (LX-2 cells) and inhibit the phosphorylation activation of the PI3K / AKT / mTOR pathway. Animal experiments show that this invention can improve liver function indicators and liver tissue pathological damage in animals with liver injury, regulate blood rheological indicators and related factor levels, and has broad application prospects. The preparation method and application of this invention are also disclosed.

A method of predicting a patient's prognosis of prostate cancer, the method comprising providing and analysing a patients germline genetic material and detecting germline variants of genes up-regulated by activation of the PI3K / AKT / mTOR pathway, genes up-regulated by activation of the PI3K / AKT / mTOR pathway, genes up-regulated by KRAS activation, genes up-regulated in response to low oxygen levels, genes regulated by NF-kB in response to tumour necrosis factor (TNF) and / or genes specifically up-regulated in pancreatic beta cells or at least one gene from Table 1. Also provided is a method of determining treatment regimen and a biomarker panel.

The invention discloses an application of disulfiram and / or irisin in preparation of a medicine for treating aconitine poisoning. It is found through a large number of attempts that disulfiram can inhibit abnormal expression of alpha-syn in central nervous system caused by aconitine, irisin can inhibit aggregation of alpha-syn, both disulfiram and irisin can rescue PI3K / Akt / mTOR pathway abnormity caused by aconitine, disulfiram or irisin is applied to dyskinesia caused by aconitine, the remarkable improvement effect can be achieved, and the application range of disulfiram or irisin is widened. And an effective strategy is provided for toxicity reduction treatment of clinical aconitine-containing drug poisoning.

The application discloses application of a SUCNR1 gene expression inhibitor in preparation of a product for preventing or treating a dairy cow dystocia. The application provides application of a substance taking a SUCNR1 protein as an inhibition target and / or a substance taking a SUCNR1 gene as an inhibition target in preparation of a product. The application of the product is as follows: promoting trophoblast cell apoptosis; inhibiting macrophage M2 type polarization; promoting trophoblast cell apoptosis by inhibiting macrophage M2 type polarization. The inventors of the application find that silencing the SUCNR1 gene can inhibit a PI3K signal pathway, thereby inhibiting macrophage M2 type polarization, thereby promoting trophoblast cell apoptosis, thereby helping to solve the problem of dystocia.

Described herein are compositions and methods for treating a disease or disorder associated with PI3K signaling. For example, such compositions can include use of modulators of glucose metabolism, use of at least one kinase in the insulin-receptor / PI3K / AKT / mTOR pathway, and / or use of diet that influences the subject's metabolic state.

The present application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating prostate cancer and a preparation method thereof. The traditional Chinese medicine composition is prepared from raw materials including the following components by weight: cassia twig 5-50 parts, poria 5-50 parts, cortex moutan 3-30 parts, red peony root 3-30 parts, persicae semen 3-30 parts, fructus psoraleae 1-20 parts, and drynaria 1-20 parts. The present application proves through experiments that the traditional Chinese medicine composition can effectively inhibit the proliferation, migration and invasion of prostate cancer cells. Through extensive transcriptome analysis, it is found that the traditional Chinese medicine composition inhibits the expression of key genes such as HSP90AA1 and CDK1, and regulates the PI3K signal pathway and AR signal transduction in the prostate cancer pathway to achieve inhibition of prostate cancer. Therefore, the traditional Chinese medicine composition has a good application prospect.

The invention discloses an application of a low molecular weight protein GRAB-L as a PI3K signal channel activator. An in-vivo experiment shows that the protein GRAB-L serving as an effective component in the bitter gourd-derived extracellular vesicles can obviously reduce fasting blood glucose and postprandial blood glucose of mice, obviously reduce blood fat, relieve fatty degeneration of livers, improve the insulin secretion level and reduce the content of autoantibodies in serum of type 1 diabetes mellitus (T1DM) mice to a certain extent; as a PI3K activator, the compound can activate PI3K phosphorylation and PI3K / AKT / FOXO1 / GSK3beta signal channels, inhibit liver glycogen synthesis and gluconeogenesis, increase glycogen decomposition, glycolysis and the like to improve liver dysfunction and maintain glucose homeostasis, and has great significance in treatment of diabetes mellitus.

The invention discloses an exosome-loaded polypeptide and application thereof in treating polycystic ovarian syndrome. The exosome loaded polypeptide is a mesenchymal stem cell exosome loaded with 740Y-P polypeptide obtained by adding a section of anchor peptide to the tail end of a PI3K signaling pathway agonist 740Y-P polypeptide and connecting the polypeptide with a mesenchymal stem cell exosome surface mask protein. The exosome-loaded polypeptide disclosed by the invention can be used for preparing medicines for treating metabolic dysfunction and / or ovulation disorder caused by polycystic ovarian syndrome.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a CDCA5 inhibitor in preparation of a medicine for treating ovarian cancer. According to the invention, CDCA5 is knocked out from UWB1.289 and snu251 cells, and Olaparib, MHY1485 or 740Y-P is given to the UWB1.289 and snu251 cells. CCK-8, immunofluorescence staining, a transmission electron microscope and western blot are used for detecting cell viability, autophagy, DNA damage and a PI3K / AKT / mTOR pathway. And establishing a BRCA1 mutation ovarian cancer xenotransplantation tumor model. The overall influence of CDCA5 knockout and olaparib is evaluated through tumor volume, weight and biomarkers. Research results show that knock-down CDCA5 is combined with olaparib to inhibit growth of ovarian cancer with BRCA1 mutation, and autophagy and DNA damage are promoted through a PI3K / AKT / mTOR pathway.

The present invention belongs to the field of biomedicine, and specifically relates to the application of BUB1 in the diagnosis and treatment of cervical cancer. The present invention found that BUB1 expression was significantly elevated in cervical cancer patients, particularly in cervical squamous cell carcinoma and endocervical adenocarcinoma, indicating that BUB1 can be used as a diagnostic marker for cervical cancer. Knockdown of the BUB1 gene can inhibit the proliferation of cervical cancer cells and induce apoptosis of cervical cancer cells. BUB1 regulates cervical cancer cell autophagy by regulating the PI3K / AKT / mTOR pathway during the formation and degradation of autophagosomes. Knockdown of the BUB1 gene can inhibit cervical cancer cell autophagy, increase cervical cancer cell apoptosis, and partially reverse cell apoptosis by inhibiting mTOR function. Animal model experiments have also demonstrated that knockdown of BUB1 can significantly inhibit the growth of subcutaneously transplanted tumors.

The invention discloses a preparation method and application of a Tibetan osbeckia concave ethanol extract, and belongs to the technical field of extraction of active ingredients of natural medicines. The method comprises the following steps: drying and crushing the whole herb of the passiflora foetida, heating, refluxing and extracting by using an ethanol solution with the volume fraction of 50-95%, combining extracting solutions, concentrating under reduced pressure, and freeze-drying to obtain the extract. The extract is rich in phenolic acid, coumarin and flavonoid active ingredients, the total flavonoid content is larger than or equal to 15%, the total coumarin content is larger than or equal to 8%, and the extract has remarkable antioxidant and anti-inflammatory activity. Experiments show that the extract can inhibit oxidative stress by regulating an HO-1 / Nrf2 signal channel and relieve inflammatory response by regulating an Myd88 / AKT / PI3K signal channel, and is suitable for treating chronic atrophic gastritis (CAG). In addition, when the concentration of the extract is 25 mu g / mL, the scavenging rate of DPPH free radicals reaches 50%, and release of inflammatory factors TNF-alpha, IL-6 and NO can be remarkably inhibited. The invention provides a new way for developing natural medicines for treating CAG and antioxidative and anti-inflammatory medicines.

The present invention provides a derivative having a tetravalent platinum structure of cetirizine, as well as its preparation method and use. The compound having a tetravalent platinum structure of cetirizine is represented by general formula (I), wherein, #imgabs0#, #imgabs1# is selected from cisplatin or oxaliplatin; L is a hydroxyl group or #imgabs2#. The tetravalent platinum structure of cetirizine described in the present invention inhibits histamine (HA) secretion in tumors through the functional group cetirizine, blocks the HA / HRH1 signaling axis, inhibits the PI3K / AKT / mTOR pathway, and thereby inhibits tumor angiogenesis; induces DNA damage through the platinum nucleus; and the two synergistically exert anti-tumor effects. The compound has significant anti-tumor ability, especially excellent therapeutic effects on metastatic malignant tumors. It is expected to provide a new drug candidate for the clinical treatment of tumors and a new direction for the research and development of new platinum drugs and anti-metastatic malignant tumor drugs.

The present disclosure relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof and (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof. The present disclosure also relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof, (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof, and (3) a third agent which is an agent that regulates the PI3K / Akt / mTOR pathway or a pharmaceutically acceptable salt thereof.

The invention belongs to the technical field of biological medicines, and discloses an application of ACSS1 as a target in screening / preparing a medicine for treating renal clear cell carcinoma, and an application of a reagent for inhibiting expression of ACSS1 in preparing a medicine for treating renal clear cell carcinoma. The invention also discloses application of a reagent for detecting ACSS1 expression in preparation of a kit for diagnosing renal clear cell carcinoma or prognosis of renal clear cell carcinoma. Experiments prove that by knocking down ACSS1, the expression level of a tyrosine kinase receptor EphA2 can be lowered, growth of the renal clear cell carcinoma is inhibited, a new target is provided for treatment of the renal clear cell carcinoma, PI3K / AKT / mTOR pathway activation can be inhibited by inhibiting EphA2, then proliferation, migration and metabolism of cells are regulated and controlled, and therefore the purpose of relieving or treating the renal clear cell carcinoma is achieved. The invention provides a new direction and thought for the treatment of the clear cell renal carcinoma, and is expected to be applied to the research and development of new drugs for treating the clear cell renal carcinoma.

The present disclosure relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof and (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof. The present disclosure also relates to a pharmaceutical combination comprising (1) a first agent which is a CDK inhibitor or a pharmaceutically acceptable salt thereof, (2) a second agent which is an anti-hormonal agent or a pharmaceutically acceptable salt thereof, and (3) a third agent which is an agent that regulates the PI3K / Akt / mTOR pathway or a pharmaceutically acceptable salt thereof.