39 results about "PI3K signaling" patented technology

The present invention is directed to the administration of an HSV derived oncolytic virus and a PI3K / AKT / mTOR pathway inhibitor to treat various types of resistant tumors. Therapy-resistant tumor formation is one of the main causes for treatment failure in the clinic. The treatment methods and compositions disclosed herein sensitize resistant tumors to the treatment of herpes simplex virus (HSV)-based oncolytic virotherapy. Pre or co-treatment of resistant tumor cells with the mTOR inhibitor, rapamycin, or certain PI3K inhibitors, such as LY294002, can efficiently sensitize the tumors to HSV derived oncolytic viruses, whereby the replication and spread of the viruses are dramatically enhanced.

The present invention provides methods, compositions, and combinations for treating cancer via combined use of a compound of formula (I), and / or their subgenra, or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R8, R9, R11a, R11b, R11c, and R11d are as defined herein, and at least one therapeutically active agents selected from inhibitors of PI3K / AKT / mTOR pathway, active agents associated with the treatment of prostate cancer, and anticancer agents.

The present invention provides methods for detecting, measuring and quantitating the activation states of components of the PI3K signaling pathway in cells such as tumor cells. In particular embodiments, the present invention enable the determination of tumor adaptation to anticancer therapy. Accordingly, the present invention provides methods for improved cancer therapy selection / adjustment and disease monitoring.

The invention discloses application of a small molecule inhibitor DHW-5 of methane sulfonamides in preparation of antitumor drugs, and belongs to the technical field of biological medicine. Accordingto the application, a drug DHW-5 which can effectively inhibit the growth of tumor cells is screened out from small molecule inhibitor libraries of the methane sulfonamides, and can effectively inhibit the proliferation of cervical cancer hela cells, breast cancer BT549 cells, non-small cell lung cancer A549 cells, ovarian cancer SKOV-3 cells and gastric cancer cells SGC-7901, the semi-inhibitoryconcentration are all lower than 9.0 uM, and particularly, the inhibition effect on the breast cancer BT549 cells is the best. The inhibitor can target phosphoinositide 3kinase (PI3K), block the conduction of PI3K signaling pathways, and trigger cycle arrest and endogenous pathways mediated by mitochondria so as to induce apoptosis of the tumor cells. The inhibitor can be used for preparing the antitumor drugs and provides a new idea and mechanism for the research and development of antitumor small molecule drugs of kinase inhibitors.

The present application relates to a citrus black tea extract. The citrus black tea extract comprises tea polyphenols, free amino acids, flavonoid compounds, soluble sugars, theaflavins, thearubiginsand theabrownin.The citrus black tea extract has relatively strong anti-oxidation, anti-cell proliferation-and-migration activities, and can be used to prepare PI3K signaling pathway inhibitors or MMPs signaling pathway inhibitors.

The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and / or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K / AKT / mTOR pathway. Advantageously, these compounds perform as dual PI3K / mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and / or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K / AKT / mTOR pathway. Advantageously, these compounds perform as dual PI3K / mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

The present invention provides methods for detecting, measuring and quantitating the activation states of components of the PI3K signaling pathway in cells such as tumor cells. In particular embodiments, the present invention enable the determination of tumor adaptation to anticancer therapy. Accordingly, the present invention provides methods for improved cancer therapy selection / adjustment and disease monitoring.

The invention relates to the field of medicines, in particular to a compound or pharmaceutically acceptable salt, isomer, prodrug, polymorphic substance or solvate thereof. The invention provides a compound or a pharmaceutically acceptable salt, isomer, prodrug, polymorph or solvate thereof. The chemical structural formula of the compound is shown as a formula I or a formula II. The compound provided by the invention is a new compound extracted from a natural product; the compound can be extracted from a daphne genkwa extract, can be applied to PI3K / Akt / mTOR pathway mediated inhibition of proliferation of tumor cells (such as colon cancer cells), and shows very good anti-proliferation and apoptosis-promoting activity, so that the compound has a good industrialization prospect.

The invention belongs to the field of pharmaceutical and chemical industries and relates to a compound as shown in a general formula I, a pharmaceutical salt or a hydrate of the compound, a preparation method of the compound as shown in the general formula I, a pharmaceutical composition containing the compound as shown in the general formula I or the pharmaceutical salt or the hydrate of the compound and an application of the compound as shown in the general formula I or the pharmaceutical salt or the hydrate of the compound in production of drugs, wherein the compound as shown in the generalformula I has an effect on inhibiting a PI3K / Akt / mTOR signal pathway of a mammal, all substituent groups in the general formula I are defined as the specification, and the drugs are used for treatingdiseases caused by abnormal expression of the PI3K / Akt / mTOR signal pathway of the mammal.

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 PI3Kalpha selective inhibitor and a preparation method and application thereof, a triazine ring benzoxazole compound and a preparation method and application thereof, and the structural formula of the compound is shown as a formula I or a pharmaceutically acceptable salt thereof. Biochemical activity tests show that the compounds have good inhibitory activity on PI3K alpha, so that the compounds can provide effective inhibitors with better selectivity for treatment of diseases regulated by PI3K, and target drugs for treating diseases related to PI3K signal pathways, such as gastric cancer, breast cancer, ovarian cancer and leukemia, are expected to be developed.

The invention discloses application of a TNFSF15 protein as a lymphocyte immunopotentiator and an activation method of the TNFSF15 protein, belonging to the technical field of medicines. According to the invention, the TNFSF15 protein can be used as the lymphocyte immunopotentiator to promote lymphocyte immune cells such as B cells and CD8<+>T cells to infiltrate tumors, promote anti-tumor immune response and inhibit tumor growth; the TNFSF15 also promotes proliferation of B cells and activates expression of ICOSL by activating an NF-kappa B signal, so the CD8<+>T cells are promoted to secrete GZB so as to play a tumor killing role; and meanwhile, a PI3K signal channel participates in TNFSF15 to promote CD8<+>T cells to secrete the GZB. The TNFSF15 protein provided by the invention has obvious effects on in-vitro amplification and T cell killing activation of immunotherapy, and provides more possibilities for immunotherapy of tumors.

The invention discloses an application of arsenic trioxide to treatment of gastrointestinal stromal tumor. The arsenic trioxide is used for preparing an arsenic trioxide-containing drug for treating imatinib-resistant gastrointestinal stromal tumor, and can improve the sensitivity of gastrointestinal stromal tumor to imatinib and promote cancer cell apoptosis by inhibiting cell proliferation related PI3K / AKT / mTOR pathways. The arsenic trioxide can overcome the drug resistance of the gastrointestinal stromal tumor to the imatinib, and has good hygienic and economic effects.

The invention discloses a regulating effect of zuojin wan (ZJW) on a ROCK / PTEN / PI3K signal pathway of human gastric cancer drug-resistant cells and application of ZJW. The influence of ROCK and PI3K signals on ZJW inducing apoptosis and a cycle of the gastric cancer drug-resistant cells is inhibited, and the results show that ZJW can induce apoptosis of SGC7901 / DDP cells. No significant change occurs when Y27623 is applied alone. Apoptosis induction of ZJW and Y27623 combination to the SGC7901 / DDP cells is significantly lower than that of ZJW alone, and it is indicated that activation of the ROCK signals is an important factor for ZJW to induce apoptosis. LY294002 applied alone significantly increases apoptosis of the SGC7901 / DDP cells, and it is indicated that the PI3K signals are inhibitory signals of apoptosis. The induction effect of apoptosis of the SGC7901 / DDP cells by combined use of ZJW and LY294002 is further increased rather than ZJW alone, and it is indicated that the two treatment methods have a synergistic effect.

The invention illuminates the inhibition effect and mechanism of celastrol on glioma vasculogenic mimicry for the first time. Observation by PAS-CD31 double-staining method indicates that celastrol can inhibit the formation of nude mouse tumor tissue VM (vasculogenic mimicry) and also can lower the expression of naked mouse glioma mimicry related proteins EphA2 and VE-cadherin, and in-vitro experiments verify that celastrol can inhibit the formation of U87 and U251 glioma cell VM through a PI3K / AKT / mTOR pathway.

This invention provides compounds of the formula (I):wherein Y1, Y2, Z, X1, X2, and W′ are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and PI3K / AKT / mTor signaling pathway kinases-mediated diseases or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3-ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROS1; MAPK pathway kinases selected from ARAF, BRAF, CRAF, ERK1 / 2, MEK1, MEK2, MEK3, MEK4, MEK5, MEK6, and MEK7; and PI3K / AKT / mTor pathway kinases: selected from mTor, PI3K α, PI3K β, PI3K γ, and PI3K δ.

The invention relates to application of a c-Src / PI3K signal channel in reproductive injury protection, and relates to the technical field of biotechnology and medicine. The invention provides an application of a c-Src / PI3K signal channel as a target spot in preparation of drugs for treating reproductive injury, and provides a new action target spot for developing natural spermatogenic drugs.

The invention relates to the technical field of medicines, and particularly relates to a compound and a preparation method and application thereof. The compound has a structure shown as a formula I in the specification, is screened out by a computer simulation and molecular docking technology, and has the effects of inhibiting a PI3K (phosphatidyl inositol 3-kinase) path and inhibiting growth and activity of tumors, and the capability of inducing tumor cell apoptosis according to confirmations. Experiments show that the compound can apparently inhibit expression of key enzyme and phosphorylation in the PI3K signal path, the inhibition function has obvious time dependency and concentration dependency, and furthermore, experiments prove that the compound cannot inhibit the key enzyme in other metabolic pathways, but can inhibit the PI3K signal path specifically.

The invention provides a high morpholine compound, a preparation method, a pharmaceutical composition and application. The general formula of the high morpholine compound or pharmaceutically acceptable salt thereof is shown as (I). The high morpholine compound provided by the invention has an obvious proliferation inhibition effect on cancer cells, especially a human prostate cancer cell line PC3, a human breast cancer cell line MCF-7, a human glioma cell U87, a human laryngeal squamous cell carcinoma cell line SNU1076 and the like, and blocks the cell cycle at the G1 phase; the phosphorylation level of key protein in a PI3K / AKT / mTOR pathway is effectively inhibited on the molecular level, and the compound has the potential of being prepared into a novel anti-tumor drug and has a good market prospect.

Primitive follicle activator and its application in human ovarian cortex culture fluid, composed of mTOR signaling pathway activator and PI3K signaling pathway activator, said mTOR signaling pathway activator includes mTOR signaling pathway activator I, mTOR signaling pathway activator I is 50-200 μM phosphatidic acid; the PI3K signaling pathway activator includes PI3K signaling pathway activator II, and the PI3K signaling pathway activator II is 100-1000 μg / mL 740Y-P. The development of this new type of culture medium is more conducive to the clinical promotion of in vitro activation of primordial follicles, expands the scope of treatment indications, and is widely used in the field of assisted reproduction to treat diseases caused by insufficient follicle reserves such as premature ovarian failure and low ovarian function.

The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and / or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K / AKT / mTOR pathway. Advantageously, these compounds perform as dual PI3K / mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

The invention discloses an application of a GnRH II type antagonist in inhibiting proliferation of progesterone-resistance endometrial cancer cells. Tests prove that the GnRH II type antagonist, when used independently or used in a mode of being combined with MPA, can be used for inhibiting the growth of the endometrial cancer cells, in particular the growth of the progesterone-resistance endometrial cancer cells; and by up-regulating PR expression, inhibiting a PI3K signal path and other mechanisms and by reversing progesterone resistance, the sensitivity of a progesterone-resistance endometrial cancer cell line to progesterone is enhanced.

The invention provides a 1-styryl isoquinoline derivative and a preparation method thereof, and the 1-styryl isoquinoline derivative is synthesized by using 1-methylisoquinoline and a benzaldehyde compound as raw materials through an intermolecular nucleophilic addition elimination reaction under the catalysis of p-toluenesulfonamide. The 1-styryl isoquinoline derivative prepared by the invention has good anti-gastric cancer activity, blocks a cell cycle in a G2 / M period, and induces cell apoptosis by inhibiting a PI3K / Akt / mTOR pathway. The compound has good cytotoxicity to tumor cells, is simple to synthesize and can be applied to preparation of gastric cancer treatment drugs.

The invention provides an application of an ER beta selective agonist in tumor resistance. At present, no valuable discovery is provided for finding a new target spot for treating the targeted squamous cell carcinoma, and in addition, clinical treatment medicines for the squamous cell carcinoma are poor in effectiveness, so that the finding of the new target spot for the targeted treatment of the squamous cell carcinoma and the development of the medicines for the targeted treatment of the squamous cell carcinoma have important significance. According to the application disclosed by the invention, the lung squamous cell carcinoma resisting effect of a natural compound library is screened, and the condition that the ER beta selective agonists liquiritigenin and (-)-(S)-equol have a remarkable effect on resisting the progress of lung squamous cell carcinoma is found. Experiments also show that liquiritigenin can induce apoptosis of lung squamous carcinoma cells by inhibiting a PI3K / Akt / mTOR pathway. Meanwhile, nude mouse in-vivo experiments also prove the anti-lung squamous cell carcinoma effect of liquiritigenin. Reference is provided for developing new targets for treating squamous cell carcinoma, especially lung squamous cell carcinoma, certain reference is provided for clinical medication of lung squamous cell carcinoma patients, and in addition, the molecular mechanism of liquiritigenin for treating lung squamous cell carcinoma is clarified.

The invention relates to the technical field of biology, in particular to an application of Tubastatin A in preparation of an in-vitro activating agent for primordial follicles. The invention provides the application of the small molecular drug Tubastatin A in preparation of a primordial follicle activated preparation. Experiments show that Tubastatin A promotes precursor granulosa cells to grow and differentiate into granulosa cells by improving mTOR total protein and phosphorylation level, and KITL secreted by Tubastatin A is increased at the same time. The ligand KITL is combined with a receptor on an oocyte membrane to activate a PI3K signal in an oocyte, up-regulate the phosphorylation level of AKT and promote the activation of primitive follicles, so that the number of primary follicles is increased.

This invention provides compounds of the formula (I):wherein Y1, Y2, Z, X1, X2, and W1 are defined in the specification. These compounds are useful in the treatment of tyrosine kinases, MAPK signaling pathway kinases and PI3K / AKT / mTor signaling pathway kinases-mediated diseases or conditions, such as neurodegeneration, neuroprotection, cancer, autoimmune as well as other diseases and conditions associated with the modulation of tyrosine kinases selected from FYN, FYN Y531F, FLT3, FLT3-ITD, BRK, ITK, FRK, BTK, BMX, SRC, FGR, YES1, LCK, HCK, RET, CSK, LYN, and ROS1; MAPK pathway kinases selected from ARAF, BRAF, CRAF, ERK1 / 2, MEK1, MEK2, MEK3, MEK4, MEK5, MEK6, and MEK7; and PI3K / AKT / mTor pathway kinases: selected from mTor, PI3K α, PI3K β, PI3K γ, and PI3K δ.

The invention relates to the technical field of medicines, and particularly relates to a compound and a preparation method and application thereof. The compound has a structure shown as a formula I in the specification, is screened out by a computer simulation and molecular docking technology, and has the effects of inhibiting a PI3K (phosphatidyl inositol 3-kinase) path and inhibiting growth and activity of tumors, and the capability of inducing tumor cell apoptosis according to confirmations. Experiments show that the compound can apparently inhibit expression of key enzyme and phosphorylation in the PI3K signal path, the inhibition function has obvious time dependency and concentration dependency, and furthermore, experiments prove that the compound cannot inhibit the key enzyme in other metabolic pathways, but can inhibit the PI3K signal path specifically.