44results about How to "Inhibit autophagy" patented technology

A method for inhibiting the autophagy of motor neurons in a subject is provided. The method comprises administrating to the subject an effective amount of an active ingredient selected from the group consisting of a compound of formula (I), a pharmaceutically acceptable salt of the compound, a pharmaceutically acceptable ester of the compound and combinations thereof:wherein A is a C1-C5 alkyl optionally having one or more unsaturated bonds and optionally being substituted by one or more substituents selected from a group consisting of —OH, ═O and C1-C3 alkyl; X is H, —OH,Y is O or S and can optionally combine with A to form a five-membered ring; and R1 is H or a substituted or unsubstituted C1-C20 alkyl, wherein one or more —CH2— of the C1-C20 alkyl are optionally being replaced by —NH— or —O—.

The invention discloses a cell autophagy inhibitor taking rubiaceae-type cyclopeptides as effective components. The cell autophagy inhibitor is particularly used for inhibiting KRAS mutation, particularly KRAS dependent tumor cell protective autophagy, and promoting tumor cell apoptosis. The inhibitor is preferably a nano-micelle injection and can be applied to preparation of medicines for treating and preventing KRAS related cancers such as colon cancers, rectal cancers, lung cancers and pancreatic cancers. The cell autophagy inhibitor can effectively inhibit tumor cell protective autophagy, the rubiaceae-type cyclopeptides serving as the effective components are wide in source, the extraction process is mature, dosage forms and pharmacy modes are diversified, and the inhibitor can be applied to treatment and prevention of the KRAS related cancers and has a wide clinical application prospect.

The invention provides application of a DNA tetrahedron to induction of autophagy. The DNA tetrahedron is synthesized from four single DNA strands through self-assembling, wherein the sequences of thefour single DNA strands are shown in SEQ ID No. 1-4. The DNA tetrahedron can activate a PI3K / AKT / mTOR signaling pathway so as to conduct induction effect on autophagy. Specifically, the DNA tetrahedron can act on the upstream protein AKT of mTOR and conducts inhibition effect on the expression of the protein mTOR by activating the expression of AKT; meanwhile, DNA tetrahedron can negatively act on mTOR by up-regulating the expression of the upstream protein PI3K of mTOR so as to allow the expression of mTOR to be inhibited, so autophagy is further induced and biomolecules in cells are highlyrecycled for the cells, and thus, the proliferation and migration of cells are improved.

The invention discloses an application of ligustilide as an adjuvant drug of antitumor drugs. The research found that ligustilide can directly inhibit autophagy and then can perform combined effects with the antitumor drugs such as tamoxifen, cis-platinum and the like, the antitumor effect is improved, and the drug resistance of tumor cells to the antitumor drugs can be improved.

Belonging to the field of medicine preparation, the invention in particular relates to application of berberine in preparation of drugs inhibiting subcutaneous adipose and visceral adipose cell autophagy. The invention takes high fat fed mice as experimental objects to test whether berberine inhibits autophagy of subcutaneous adipose and visceral adipose cells of the mice. Specifically, the process includes: feeding C57BL / 6 mice with high fat for 12 weeks, then dividing the mice into a high fat group and a berberine group, continuing the high fat diet and berberine gavage once a day for 4 weeks, using Western Blot to detect the change of autophagy related protein, and using Real-time PCR to detect the change of the corresponding mRNA level. Results show that: under high fat feeding, subcutaneous and visceral adipose tissue autophagy increases, and berberine could effectively inhibit subcutaneous adipose and visceral adipose autophagy of the high fat fed mice, thus providing the experimental data and theoretical basis for more reasonable application of berberine in treatment of obesity clinically.

The invention provides a nano-medicine, a preparation method thereof and an application of the nano-medicine. The nano-medicine comprises a calcium phosphate substrate, a chemotherapy medicine, a photo-thermal agent and an autophagy inhibitor, the chemotherapy medicine is sealed in the calcium phosphate substrate, the surface of the calcium phosphate substrate is modified by the photo-thermal agent, and the autophagy inhibitor is loaded into a pore of the photo-thermal agent. According to the nano-medicine, chemotherapy and thermotherapy are combined, calcium phosphate serves as a rigid substrate, the chemotherapy medicine and the photo-thermal agent are sealed in the rigid substrate of the calcium phosphate, the autophagy inhibitor of a cell is loaded on the rigid substrate, so that chemotherapy and thermotherapy effects can be improved by inhibiting autophagy, and tumor treatment effects are improved.

The present invention provides a pharmaceutical composition for treating digestive tract cancers, belongs to the technical field of drugs and an application of FTY720 or a combination of the FTY720 with JTE-013 in preparation of 5-fluorouracil (5-FU) drug resistance reversal agents. The provided pharmaceutical composition for treating the digestive tract cancers comprises 5-fluorouracil and at least one of the following 5-fluorouracil drug resistance reversal agents: FTY720 and JTE-013. The present invention also provides use of SphK2 and S1PR2 in screening drugs for reversing drug resistanceof fluorouracil compounds for the digestive tract cancers. The SphK2 up-regulates DPD expression-induced fluorouracil primary drug resistance and S1PR2 translocation-induced fluorouracil acquired drugresistance, and besides, the SphK2 and S1PR2 can be used as new molecular targets by designing targeted drugs to solve a drug resistance problem of the fluorouracil and derivatives thereof in cancertreatment processes.

The invention discloses new use of a 3, 4-broken cycloartane type triterpenoid compound. The compound is nigranoic acid or kadsuric acid, and is used in preparation of autophagy inhibitors and preparation of drugs for increasing the treatmnet sensitivity of anti-tumor drugs. The compound can be used for inhibiting ubiquitination modification of an autophagy receptor p62 and prevent activation of ap62 autophagy receptor function, and can inhibit the protective autophagy of tumor cells induced by anti-tumor drugs. The invention also provides an anti-tumor pharmaceutical composition, which comprises the 3, 4-broken cycloartane triterpenoid compound and an anti-tumor drug capable of easily causing tumor cell protective autophagy, can inhibit tumor cell growth and promote tumor cell death, andcan be used for treating cancers such as breast cancer and the like.

Methods of treating autophagy related diseases, e.g. cancer and malaria, using novel autophagy inhibiting agents are described.

The invention belongs to the technical field of medicinal preparations with organic and effective components, and discloses a detection method for influences of micro RNA-138-5p on human pancreatic cancer cell apoptosis under hypoxia. After up-regulation of miR-138-5p mimics, autophagy-associated protein of western blot detection experimental groups is inhibited; pancreas tumor cell autophagic vacuoles of confocal microscopy examination experimental groups are increased. The apoptotic cell percentage plus the necrotic cell percentage and differences between the groups have remarkable significance, and expression of apoptosis-associated protein of the western blot detection experimental groups is regulated up. MiR-138-5p and SIRT1 3'UTR regions are complementarily combined to inhibit reduction of SIRT1 expression. The miR-138-5p plays an important role in autophagy fluxes under hypoxia of pancreatic cancer cells, expression of SIRT1 is regulated through direct targeting to inhibit hypoxia-induced autophagy, and apoptosis of the panc-1 pancreatic cancer cells is promoted at the same time.

The invention provides application of brown algae oligosaccharide or pharmaceutically acceptable salt thereof in preparation of a medicine for treating acute kidney injury, wherein the brown algae oligosaccharide is brown algae disaccharide, brown algae triose and / or brown algae tetraose. The invention also provides application of the brown algae oligosaccharide or the pharmaceutically acceptable salt thereof in preparation of medicines for preventing acute kidney injury from being converted into chronic kidney diseases. After the brown algae oligosaccharide is used for treating an animal with acute kidney injury, the serum creatinine level is obviously reduced, the urine concentration function of the kidney is obviously recovered, the levels of renal tubular injury factors (KIM-1 and NGAL) are obviously reduced, the expression of inflammatory factors is obviously reduced, the pathological change of the kidney is obviously improved, and the treatment effect is enhanced along with the increase of the dosage. Therefore, the brown algae oligosaccharide disclosed by the invention has a relatively strong effect of treating the acute kidney injury. In addition, when acute kidney injury occurs, the brown algae oligosaccharide disclosed by the invention can be used for protecting kidney functions and preventing the acute kidney injury from being converted into chronic kidney diseases.

The invention discloses application of tanshinone I in preparation of tumor cell autophagy inducer drugs. Compared with the prior art, the invention for the first time finds that tanshinone I can induce autophagy of tumor cells and has a remarkable treatment effect on cervical cancer, breast cancer or liver cancer, especially cervical cancer. Research proves that tanshinone I can inhibit cancer cell growth, inhibit cancer cell mitochondrial injury and autophagy, and induce the expression of tumor cell autophagy molecules and cutting of autophagy molecule LC3.

The invention discloses an application of an SGLT2 inhibitor to preparation of a product for improving sensitivity of an antitumor drug. The inventor finds that the SGLT2 inhibitor Canagliflozin can inhibit the autophagy phenomenon of stress protection generated by tumor cells during chemotherapeutic drug treatment by inhibiting the expression and functions of P-glycoprotein in the tumor cells, sothat the sensitivity of the tumor cells to chemotherapeutic drugs is improved, and the treatment effect of the drug is enhanced. The inhibitor of the type can exist in the form of liquid, dry powderor extract, can be made into capsules, tablets, injections, pills, granules, powder and other various dosage forms with health-care or medicinal effects together with various conventional auxiliary materials, and can be combined with other chemotherapeutic drugs to be used for treating malignant tumors.

The invention discloses an application of ICTF (trifluoro-icaritin) to preparation of a drug for activating Akt signals and inhibiting autophagy. When ICTF is applied to a drug for treating cardiovascular diseases, it is proved that ICTF can relieve ischemia reperfusion-induced EGG damage, reduce myocardial oxidative stress of ischemia reperfusion injury, inhibit autophagy and apoptosis of myocardial cells, improve activation of the Akt signals and reduce levels of autophagy markers Beclin-1 and LC3-II. The drug for treating the cardiovascular diseases has development prospect and is especially used for treating myocardial ischemia (myocardial infarction) reperfusion injury.

The invention discloses novel medical application of tizoxanide and / or nitazoxanide and a pharmaceutically acceptable salt thereof, namely application of tizoxanide and / or nitazoxanide in the preparation of an autophagy inducer and application of drugs for treating and inhibiting diseases related to mTOR expression. According to the application, the tizoxanide and / or nitazoxanide and the pharmaceutically acceptable salt thereof can achieve related medicine effects by reducing PI3K and AKT protein phosphorylation and reducing ERK protein phosphorylation, the autophagy inhibition function in cells is reduced accordingly, and the cells are induced to achieve autophagy.

The invention discloses a medicine for treating erectile dysfunction and application thereof. The medicine for treating the erectile dysfunction comprises an inhibitor of a Wnt signal channel. The invention finds that the Wnt signal channel is a key channel activated by the fibroblast for the first time, and proves that the inhibitor using the Wnt signal channel can obviously inhibit the expression of collagen in the fibroblast derived from the cavernosum so as to inhibit the fibrosis of the penis cavernosum; therefore, the inhibitor of the Wnt signal channel has the potential of serving as the medicine for treating the erectile dysfunction, and a new thought is provided for developing the medicine for treating the erectile dysfunction.

The invention provides a combined medicine for treating malignant tumors. The combined medicine contains unit preparations with different specifications and is used for simultaneously or respectivelysupplying genetically engineered bacteria and chloroquine diphosphate salt. The combined medicine disclosed by the invention can be used for effectively treating cancers, and the effect is obviously superior to that of single use of the genetically engineered bacteria and the chloroquine diphosphate salt, so that the genetically engineered bacteria and the chloroquine diphosphate salt have an obvious synergistic effect after cooperating for use, have strong anti-tumor activity and small side effects, and provide a new treatment direction for patients who lose operation indications clinically,cannot be operated and have poor radiotherapy and chemotherapy effects.

A method for inhibiting the autophagy of motor neurons in a subject is provided. The method comprises administrating to the subject an effective amount of an active ingredient selected from the group consisting of a compound of formula (I), a pharmaceutically acceptable salt of the compound, a pharmaceutically acceptable ester of the compound and combinations thereof:wherein A is a C1-C5 alkyl optionally having one or more unsaturated bonds and optionally being substituted by one or more substituents selected from a group consisting of —OH, ═O and C1-C3 alkyl; X is H, —OH,Y is O or S and can optionally combine with A to form a five-membered ring; and R1 is H or a substituted or unsubstituted C1-C20 alkyl, wherein one or more —CH2— of the C1-C20 alkyl are optionally being replaced by —NH— or —O—.

The invention discloses an application of seneciphylline in preparation of antitumor medicines. The seneciphylline can inhibit HeLa cell proliferation and induce HeLa cell autophagy in a dose dependent and a time dependent manner. In addition, the seneciphylline inducing the HeLa cell autophagy is depended on activation of MEK / ERK1 / 2 pathway. The invention provides a novel treatment medicine of treating human cervical cancer.

The invention discloses a cell autophagy inhibitor with Rubiaceae type cyclic peptide as an active ingredient, especially for inhibiting KRAS mutation, especially KRAS-dependent tumor cell protective autophagy, and promoting tumor cell apoptosis; The inhibitor is preferably a nano-micelle injection, which can be applied to the preparation of drugs for treating and preventing KRAS-related cancers, including colon cancer, rectal cancer, lung cancer and pancreatic cancer. The autophagy inhibitor described in the present invention can effectively inhibit the protective autophagy of tumor cells. Its active ingredient Rubiaceae type cyclic peptide has a wide range of sources, its extraction process is mature, and its dosage forms and medication methods are diversified. It can be applied to the treatment of KRAS-related cancers. Treatment and prevention have broad clinical application prospects.

The invention discloses an application of ligustilide as an adjuvant drug of antitumor drugs. The research found that ligustilide can directly inhibit autophagy and then can perform combined effects with the antitumor drugs such as tamoxifen, cis-platinum and the like, the antitumor effect is improved, and the drug resistance of tumor cells to the antitumor drugs can be improved.

The invention relates to application of a curcumin analogue CD35 to preparation of a medicine for treating breast cancer. A chemical formula of the curcumin analogue CD35 is 1-(4-hydroxy-3-methoxyphenyl)-5-(2-nitrophenyl)-1,4-pentadiene-3-one, and a structural formula is shown in the description; the curcumin analogue CD35 is used for down-regulating the expression of YAP proteins in a Hippo path to inhibit the autophagy of breast cancer cells, so as to inhibit the energy metabolism of the breast cancer cells. The curcumin analogue CD35 provided by the invention has remarkable advantages of improving the targeting ability of the medicine for treating the breast cancer and reducing the toxic and side effects of the medicine.

The invention discloses an application of Abemaciclib in preparation of a medicine for treating NAFLD. After the Abemaciclib is administered to a C57BL / 6 mouse by intragastric administration for 2 weeks, histopathology and serum biochemical results show that the Abemaciclib can improve the liver lipidemia of the mouse and reduce the contents of serum ALT, AST and liver triglyceride. In-vitro experiment results show that the Abemaciclib can resist oxidative stress damage of cells through SESN2 and other mediated anti-oxidative stress pathways. In addition, our studies found that Abemaciclib caninduce HepG2 cells to form intracytoplasmic vacuoles similar to autophagy, presuming that Abemaciclib may improve NASH by inducing autophagy and inhibiting liver fibrosis.

The invention discloses a pharmaceutical composition capable of inhibiting acetylation of PINK1 of vascular endothelial cells, which is characterized in that astaxanthin is contained and also discloses the use of the pharmaceutical composition in the preparation of medicaments for preventing and / or treating cardiovascular diseases including, but not limited to, atherosclerosis, coronary heart disease, angina pectoris, cerebral thrombosis, hypertension, hyperglycemia, hyperlipidemia, myocardial infarction, ischemic cor pulmonale and the like.

The invention relates to a platinum-copper alloy / chloride ion transporter composite tumor treatment preparation and a preparation method and application thereof. The preparation method comprises the step that a chloride ion transporter is loaded to the surfaces of platinum-copper alloy nanoparticles through the electrostatic interaction. The preparation has the advantages of being good in controllability, small in side effect and the like, and the efficient tumor treatment effect can be achieved.

The present invention discloses new uses of 3,4-fragmented cyclic altine-type triterpenoids, the compounds are black schisandrin or southern schisandra, including for preparing autophagy inhibitor, preparing for increasing antitumor drug treatment A sensitive drug, the compound can inhibit the ubiquitination modification of autophagy receptor p62, prevent the activation of p62 autophagy receptor function, and can inhibit the protective autophagy of tumor cells induced by anti-tumor drugs, and the present invention also provides An anti-tumor drug composition, including 3,4-fragmented cyclic altine-type triterpenoids and anti-tumor drugs that easily induce tumor cell protective autophagy, can inhibit tumor cell growth and promote tumor cell death, and can be used for Treatment of cancers such as breast cancer.