52 results about "Akt inhibitor" patented technology

The invention belongs to the technical field of biological medicine and molecular biology, and provides application of GJB6 in preparation of an esophageal squamous cell carcinoma prognosis evaluation reagent and screening of drugs for targeted treatment of esophageal squamous cell carcinoma. The low expression of the GJB6 is applied to preparation of an esophageal squamous cell carcinoma prognosis evaluation reagent. GJB6 is low in expression in ESCC patients, and ESCC prognosis is poor. And the prognosis of patients with high expression of GJB6 is better. Overexpression of GJB6 inhibits ESCC cell proliferation, migration and invasion and in-vivo tumor enlargement. The GJB6 plays a role of a cancer suppressor gene in ESCC and inhibits cell proliferation, migration and invasion. The AKT signal channel is one of downstream channels for GJB6 to regulate the occurrence and development of ESCC. The AKT inhibitor effectively inhibits GJB6 low-expression ESCC malignant phenotypes, including enhancement of cell proliferation and migration invasion ability and in-vivo tumor enlargement. The AKT is a key therapeutic target of the GJB6 low expression type ESCC.

Disclosed herein are methods for treating cancer comprising administering to a subject a daily dose of Compound A or a pharmaceutically acceptable salt thereof in combination with an Akt inhibitor.

Disclosed herein are methods for increasing sensitivity of a cancer cell to alternating electric fields by administering an AKT inhibitor, a mammalian target of rapamycin (mTOR) inhibitor, a Phosphatidylinositol 3-Kinase (PI3K) inhibitor, and / or a Glycogen synthase kinase 3β (GSK3β) inhibitor. Disclosed are methods of increasing treatment efficacy comprising applying alternating electric fields to a target site of the subject for a period of time, the alternating electric fields having a frequency and field strength, wherein the target site comprises one or more cancer cells, and administering a therapeutically effective amount of one or more of an mTOR inhibitor, AKT inhibitor, PI3K inhibitor, or GSK3β inhibitor to the subject. Disclosed are methods of reducing viability of cancer cells using alternating electric fields for a period of time, the alternating electric fields having a frequency and field strength in combination with either an mTOR inhibitor, AKT inhibitor, PI3K inhibitor, or GSK3β inhibitor and / or a composition or compound that increases cyclin D1. Disclosed are methods of increasing apoptosis of a cancer cell comprising exposing the cancer cell to alternating electric fields for a period of time, the alternating electric fields having a frequency and field strength; and exposing the cancer cell to a PI3K inhibitor.

This disclosure relates to pharmaceutical combinations for treating and / or preventing cancer and methods and uses thereof. More particularly, provided are pharmaceutical combination comprising a PRMT5 Inhibitor and a cellular activity modulator selected from an EGFR inhibitor, a KRAS inhibitor, a KRAS-G12C inhibitor, a MEK inhibitor, a Bcl-2 inhibitor, a SOS1 inhibitor, a PARP inhibitor, a RAF inhibitor, a ERK inhibitor, a CDK4 / 6 inhibitor, a MALT1 inhibitor, a BTK inhibitor, MAT2A inhibitor, a PI3K inhibitor, a AKT inhibitor, a FGFR inhibitor, a Type I PRMT inhibitor, a STING agonist, or an immune checkpoint inhibitor / modulator.

Therapeutic methods and pharmaceutical compositions for treating a myeloproliferative neoplasm (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis, are described. In certain embodiments, the invention includes therapeutic methods of treating a MPN using a combination of a compound of Formula (I) or Formula (II) with a therapeutic agent selected from the group consisting of a JAK inhibitor, an IDH inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PD-L2 inhibitor, an interferon, a PI3K inhibitor, an AKT inhibitor, an mTOR inhibitor, a nucleoside analog, and combinations thereof.

The present specification relates to AZD9833 for use in the treatment of cancer and methods of treatment of cancer involving administration of AZD9833 wherein, in each case, the AZD9833 is administered orally once daily at a dose between 25 mg and 450 mg. AZD9833 may be administered alone or its use may be in combination with an additional anti-cancer agent such as a CDK inhibitor, everolimus or an AKT inhibitor.

Therapeutic combinations of an AKT inhibitor, a BCL-2 inhibitor and an anti-CD20 antibody are described. Preferably, the combination comprises capivasertib, venetoclax and rituximab. The combinations can be useful in the treatment of B-cell malignancies.

Therapeutic combinations of an AKT inhibitor and a BCL-2 inhibitor; an AKT inhibitor and a glucocorticoid; and an AKT inhibitor, a BCL-2 inhibitor and a glucocorticoid are described. The combinations can be useful in the treatment of acute lymphoblastic leukemia (ALL).

According to the application of the salidroside in preparation of the medicine for treating the Alzheimer's disease by relieving ferroptosis, the salidroside is used for relieving the ferroptosis of human neuroblastoma (SH-SY 5Y) cells induced by A [beta] 1-42 by inhibiting a voltage dependent anion channel 1 (VDAC1) and activating an AKT / GSK-3beta pathway, and the application of the salidroside in the preparation of the medicine for treating the Alzheimer's disease by relieving the ferroptosis of the human neuroblastoma (SH-SY 5Y) is realized by inhibiting the voltage dependent anion channel 1 (VDAC1) and activating the AKT / GSK-3beta pathway. The salidroside can relieve the ferroptosis of SH-SY 5 Y cells induced by A beta 1-42 under the optimal concentration of 30 mM. After salidroside treatment, the expression quantity of GPX 4 and FTH 1 is increased, and the expression quantity of IREB 2 is reduced. The cell apoptosis rate is reduced, and the Fe < 2 + > content and ROS level in cells are also reduced. After si-VDAC 1 is transfected, the change trend of si-VDAC 1 is similar to the trend after salidroside treatment. In addition, the treatment of an AKT inhibitor and an AKT activator shows that an AKT / GSK-3beta signal channel participates in the process of inducing the ferroptosis of the SH-SY 5 Y cells by the Abeta1-42.

The present specification relates to a method for treating a patient suffering from hormone receptor positive (HR +), human epidermal growth factor receptor 2 negative (HER2-), breast cancer, comprising administering to the patient in need thereof an oral selective estrogen receptor degrading agent (SERD) in combination with an AKT inhibitor or an mTOR inhibitor and / or a cyclin dependent kinase 4 / 6 inhibitor (CDK4 / 6i).

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes methods of recovering wild-type function to p53 mutants by treating a tumor with a compound and a second agent. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used in combination with an MDM2, PI3K, or AKT inhibitor to reduce the progression of cancers that contain a p53 mutation.

The present invention provides a CAR-T cell production method and application thereof, which belongs to the field of tumor immunotherapy technology. The present invention first prepares CAR-T cells that overexpress Runx3, and then amplifies the CAR-T cells that overexpress Runx3 in a 1μM AKTi1 / 2 environment, thereby producing a new type of CAR-T cell. Wherein Runx3 overexpression can enhance the effector function of CAR-T cells and promote CAR-T cell tumor infiltration, but does not affect the maintenance of T cell stemness that depends on AKT inhibitors. The use of AKT inhibitors can save the problem of CAR-T cells not being able to survive continuously and amplify insufficiently in vivo. The two work together and complement each other, so the new CAR-T cells produced have better long-term survival, effect and solid tumor infiltration capabilities, and thus have a stronger comprehensive ability to overcome the dilemma of solid tumors.

A unit dosage composition of an AKT inhibitor, and in particular, relates to a pharmaceutical composition in unit dosage form includes a compound of formula I-0 or a pharmaceutically acceptable salt thereof, wherein the mass of the compound I-0 or the pharmaceutically acceptable salt thereof is 5 mg to 400 mg calculated as free base.

The invention discloses application of an AKT inhibitor or an STAT3 inhibitor in preparation of a medicine for overcoming drug resistance of bladder cancer to an MEK inhibitor, and belongs to the field of biological medicine. Detecting the cell activity through an MTT method; a Western blot experiment is adopted to detect a key target protein or gene expression level, a bladder cancer drug-resistant cell ERK abnormal activation + STAT3 / Akt compensation activation mechanism is defined, p-ERK, p-STAT3 and p-Akt are locked as targets, the drug resistance of bladder cancer to an MEK inhibitor is overcome through an AKT inhibitor or an STAT3 inhibitor, the scheme can accurately inhibit abnormal pathways, reverse drug resistance and improve treatment sensitivity, and the method is safe and suitable for clinical application. A new direction is provided for patients with drug-resistant bladder cancer, and the clinical bottleneck of the MEK inhibitor is helped to be broken through.

The present application relates to dosage regimens for the treatment of cancer. The present specification relates to AZD9833 for use in the treatment of cancer and a method of cancer treatment comprising administration of AZD9833 wherein, in each case, the AZD9833 is orally administered once a day at a dose of 25 mg to 450 mg. AZD9833 can be administered alone and can also be used in combination with additional anti-cancer agents such as a CDK inhibitor, everolimus or an AKT inhibitor.

The application discloses a tricyclic quinazoline or dihydroquinazoline compound as an AKT inhibitor, a structure of the tricyclic quinazoline compound is shown in general formula I, definitions of various substituents are shown in the specification, and a preparation method of the tricyclic quinazoline compound is provided. The tricyclic quinazoline compound has significant AKT inhibiting activity and can be used as an AKT inhibitor.

The invention belongs to the technical field of medicine application and biological medicine, and particularly relates to application of an AKT inhibitor in preparation of a medicine for inducing pancreas islet transplantation immune tolerance. The invention discovers that the AKT inhibitor MK-2206 can effectively induce immune tolerance after pancreas islet transplantation for the first time, system experiments prove that a short-term intervention scheme adopting the AKT inhibitor MK-2206 can obviously promote long-term survival of pancreas islet transplantation, and the effect of the AKT inhibitor MK-2206 is superior to that of a traditional immunosuppressor. The method belongs to secondary development of medicines with known active ingredients, and provides a potential novel treatment strategy for clinical induction of transplantation immune tolerance.

The invention relates to application of an AKT inhibitor to preparation of a medicine for preventing or treating ovarian cancer, and application of the AKT inhibitor combined with other ovarian cancer treatment medicines including one or more of a PARP inhibitor, a plant chemotherapy medicine, an antibiotic chemotherapy medicine, a platinum medicine and an alkylating agent to preparation of the medicine for preventing or treating the ovarian cancer. Wherein the combined medication can effectively inhibit the growth of ovarian tumor cells and the formation of cell clone, is obviously superior to the single medication, has additive or synergistic effect, has low toxic and side effects on normal cells and high safety, provides a more effective method for treating ovarian cancer, and has important clinical value.

The invention belongs to the technical field of biology, and relates to application of chimeric polypeptide TAT-Ae alone or in combination with an AKT inhibitor in tumor treatment. Specifically, the invention discloses application of a blocking TRIB3 / AKT inhibitor targeting tumor stemness and proliferation in preparation of drugs for preventing or treating breast cancer independently or in combination with an AKT inhibitor. The amino acid sequence table of the inhibitor for blocking TRIB3 / AKT is SEQ ID No.1, and the AKT inhibitor is Oridonin. The inhibitor for blocking TRIB < 3 > / AKT can be specifically combined with TRIB < 3 >, so that the interaction of TRIB < 3 > / AKT is blocked, the protein degradation of a transcription factor FOXO1 is promoted, and finally the expression of a dry factor SOX2 is reduced; the AKT inhibitor inhibits tumor cell proliferation by inhibiting AKT activity, so that the AKT inhibitor is applied to preparation of drugs for treating and preventing breast cancer, lymphoma, lung cancer and colon cancer. The prepared medicine has the advantages of being remarkable in curative effect, small in toxic and side effect and safe to use when being used for treating tumor diseases.

The present disclosure provides certain LATS1 and / or LATS2 inhibitors, including selective LATS1 / LATS2 inhibitors and dual LATS1 / LATS2 and AKT inhibitors that are useful for the treatment of wounds, of diseases that would benefit from organ or cellular regeneration, of cancer, and of heavy metal poisoning, as well as for promoting ex vivo growth of a cell line or a cell product and for accelerating tissue growth ex vivo. Also provided are pharmaceutical compositions containing such compounds and methods of using such compounds.

The invention provides application of a small molecule compound in preparation of a product for inhibiting 3C-like cysteine protease, and belongs to the technical field of biological medicine. The small molecule compound is one or more of Gedatolisib, EGFR-IN-8, Akt inhibitor VIII, Bavlogalutamide, lifrafenib, TAM-IN-2, GSK1904529A and IKK 16, and the molecular weight of the small molecule compound is more than or equal to 100,000, the molecular weight of the small molecule compound is more than or equal to 100,000, the molecular weight of the small molecule compound is more than or equal to 100,000, the molecular weight of the small molecule compound is more than or equal to 100,000, and the molecular weight of the small molecule compound is more than or equal to 100,000. The small molecule compound provided by the invention has a remarkable inhibition effect on 3C-like cysteine protease, provides more choices for preparing a 3C-like cysteine protease inhibitor, and also provides a thought for developing antiviral drugs in the future.

A combined drug of an estrogen receptor degrader and an AKT inhibitor and use thereof. The present invention pertains to the field of pharmaceuticals. The combined drug comprises an estrogen receptor degrader and an AKT inhibitor of the same specification or different specifications that are administered simultaneously or separately and a pharmaceutically acceptable carrier, can degrade estrogen receptors, inhibit cancer cell growth, exert a synergistic inhibitory effect, and significantly improve the effect of treating estrogen receptor-related diseases, and has good application prospects.

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 present application provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of hereditary hemorrhagic telangiectasia (HHT).

This invention discloses the use of AKT inhibitors in the manufacture of drugs for the prevention or treatment of breast cancer. In particular, it provides the combination of an AKT inhibitor and fulvestrant in the manufacture of drugs for the prevention or treatment of breast cancer. The combination of an AKT inhibitor and fulvestrant can effectively inhibit the proliferation and colonization of breast cancer cells. The combination is clearly more effective than monotherapy, exhibits additive or synergistic effects, has lower toxicity and side effects to normal cells, is safer, and provides a more effective method for treating breast cancer, thus having significant clinical value.

Methods and materials involved in identifying and treating mammals having a cancer resistant to BET inhibitors are provided. For example, methods and materials for administering (a) one or more AKT inhibitors and / or one or more CDK inhibitors and / or one or more CBP / p300 inhibitors in combination with (b) one or more BET inhibitors to mammals identified as having a cancer resistant to treatment with one or more BET inhibitors in the absence of AKT, CDK, and CBP / p300 inhibitors are provided.

The invention relates to application of an AKT inhibitor in preparation of drugs or cosmetics for inhibiting melanogenesis. According to the present invention, the AKT inhibitor is CCT128930. Arsenic exposure enables the phosphorylation level of PI3K / AKT signal channel protein to be improved, CCT128930 enables the phosphorylation level of the channel protein to be inhibited, and meanwhile melanin inhibition caused by arsenic is also improved in the process.

The invention discloses application of an AKT inhibitor in preparation of a medicine for preventing or treating breast cancer. In particular, the invention provides application of an AKT inhibitor combined with fulvestrant in preparation of medicines for preventing or treating breast cancer. The AKT inhibitor and fulvestrant are combined to effectively inhibit the growth of breast tumor cells and cell clone formation, the combined effect is obviously superior to that of single medication, the additive or synergistic effect is achieved, meanwhile, the toxic and side effects on normal cells are low, the safety is high, a more effective method is provided for treating breast cancer, and the important clinical value is achieved.