70 results about "Akt inhibitor" patented technology

The present invention relates to a method of treating cancer by administering an IGF-1R specific antibody in combination with an anti-cancer agent exemplified by an Akt pathway inhibitor. The first and second amounts together comprise a therapeutically effective amount.

The present invention relates to biomarkers of use in cancer therapy, wherein the therapy comprises treatment with anti-Trop-2, anti-CEACAM5 or anti-HLA-DR ADCs (antibody-drug conjugates), alone or in combination with and one or more anti-cancer agents, such as a DDR inhibitor, an ABCG2 inhibitor, a microtubule inhibitor, a checkpoint inhibitor, a PI3K inhibitor, an AKT inhibitor, a CDK 4 inhibitor, a CDK 5 inhibior, a tyrosine kinase inhibitor or a platinum-based chemotherapeutic agent. Preferably, the combination therapy has a synergistic effect on inhibiting tumor growth. The biomarkers are of use to predict efficacy and / or toxicity of ADC therapy, determine tumor response to treatment, identify minimal residual disease or relapse, determine prognosis, stratify patients for initial therapy or to optimize treatment for the patient, based on the specific biomarkers detected.

A treatment for cancer using a combination therapy including an inhibitor of the PI3K / Akt pathway in combination with roscovitine. It is shown that the combination of roscovitine and API-2 (Triciribine) or roscovitine and LY294002 induce the apoptosis of androgen-dependent (LNCaP) and androgen-independent (PC3) prostate cancer cells. Two important results have been observed. First, cells that respond to roscovitine alone (LNCaP) initiate apoptosis sooner when co-treated. Second, cells that do not respond to roscovitine alone (PC3) apoptose when co-treated, although with delayed kinetics. In the absence of roscovitine, AKT inhibitors had no effect on LNCaP or PC3 survival, and in both cell lines, the combined treatment activated the mitochondrial pathway of apoptosis. Importantly, normal epithelial cells (RPWE) remained viable in the presence of roscovitine and AKT inhibitors. Events elicited by roscovitine (down-regulation of XIAP) and AKT inhibitors (accumulation of Bim) in LNCaP and PC3 cells are identified. Additional data show that PC3 cells apoptose when treated with AKT inhibitors and depleted of either XIAP or Cdk9. Taken together, these important results lead to improved treatments for cancers, such as prostate cancer, through the combination therapies taught herein.

The present invention provides (1) an agent for the prevention or treatment of an estrogen receptor-negative and HER2-negative breast cancer comprising an Akt inhibitor, (2) an agent for the prevention or treatment of an estrogen receptor-negative, progesterone receptor-negative and HER2-negative breast cancer comprising an Akt inhibitor, (3) a method of screening an agent for the prevention or treatment of a breast cancer which is negative for hormone receptors such as an estrogen receptor, a progesterone receptor, etc. and is negative for HER2, which comprises using an Akt inhibitory activity as an indicator; and so on.

The invention relates to a 5-thiazole amide compound and biology application thereof. The 5-thiazole amide compound has a general formula (I) described in the specification and is used for targeting an AKT / PKB kinase (ATP binding site). Experiments prove that a thiazole amide AKT inhibitor can remarkably inhibit the activity of the AKT kinase in vitro and has strong proliferation inhibition function on various tumor cells with high AKT activity, which indicate that the 5-thiazole amide compound can be used for preparing drugs for resisting tumors.

Disclosed herein is a species of peptide and non-peptide inhibitors of Akt, an oncogenic protein. Beginning with a residue of Akt target substrate GSK-3, the functional domains of the GSK-3 residue were characterized. Functionally homologous non-peptide groups were substituted for the amino acids of the GSK-3 creating a hybrid peptide-non-peptide and non-peptide compounds capable of binding to Akt. The non-peptide compounds show increased stability and rigidity compared to peptide counterparts and are less susceptible to degradation. The bound non-peptide compounds exhibit an inhibitory effect on Akt, similar to peptide-based Akt inhibitors.

The invention discloses an anti-tumor combination and the application thereof; the anti-tumor combination which includes effective dose of platinum-based chemotherapy and AKT inhibitor and / or p70S6K1 inhibitor has the function of inhibiting the drug resistance of the tumor to the platinum-based chemotherapy, improves the effects of anti-tumor drugs, and can be used for preparing drugs that can resist various tumors, such as lung cancer, ovarian cancer, prostate cancer, breast cancer, stomach cancer, nasopharyngeal cancer, esophageal cancer, malignant lymphoma, head and neck squamous cell carcinoma, thyroid cancer, osteosarcoma, etc.

4-[5-(2-Amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol or a pharmaceutically acceptable salt thereof or a hydrate of the compound or the salt thereof as Akt inhibitors that are antineoplastic and / or antiviral agents as well as compositions comprising these compounds and methods of using these compounds.

The invention relates to an antitumor polypeptide for targeted inhibition on an ERK signal channel and application of the antitumor polypeptide. According to the antitumor polypeptide, a micro-molecule polypeptide for targeted inhibition on the ERK signal channel is established; a series of biological experiment shows that the micro-molecule polypeptide is capable of effectively inhibiting drug resistance of a PI3K / AKT inhibitor or a paclitaxel medicine in the antitumor treatment process for multiple tumors such as prostate cancer, breast cancer, colon cancer and rectal cancer, and has a remarkable synergic antitumor function; as the ERK signal channel exists in multiple tumors and is one of important signal channels for promoting cell growth and tumor generation and development, the micro-molecule polypeptide can be used for treating the tumors, and preferably the micro-molecule polypeptide is used together with the PI3K / AKT inhibitor or the paclitaxel medicine.

Disclosed are new members of a class of non-lipid small molecule inhibitors which interfere with the interaction between phosphoinositol-3,4,5-triphosphate (PIP3) and pleckstrin homology (PH) domains. These molecules target a broad range of PIP3-dependent signaling events in vitro and exert significant anti-tumor activity in vivo, with improved activity and selectivity toward particular PH domains. The small molecule inhibitors of the invention can be used alone or together with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or other cancer medicament to treat cancer. Small molecule inhibitors of the invention act synergistically in combination with TRAIL and with other Akt inhibitors in treating cancer. Pharmaceutical compositions and methods for treating cancer are provided.

Provided herein are methods for delaying or inhibiting T cell maturation or differentiation in vitro for a T cell therapy, comprising contacting one or more T cells from a subject in need of a T cell therapy with an AKT inhibitor and at least one of exogenous Interleukin-7 (IL-7) and exogenous Interleukin-15 (IL-15), wherein the resulting T cells exhibit delayed maturation or differentiation. In some embodiments, the method further comprises administering the one or more T cells to a subject in need of a T cell therapy.

The invention relates to a method of inducing Foxp3 expression in a T cell comprising (i) stimulating a T cell (ii) inhibiting signalling via PBK alpha or PBK delta or m-TOR or Akt in said T cell, wherein said inhibition is commenced 10 to 22 hours after the stimulation of (i). The invention also relates to certain uses of PBK inhibitors, PBK inhibitors for particular uses, and kits.

The invention discloses an application of an Akt inhibitor in preparation of a drug for treating platelet number decrease related diseases. Experiments prove that Akt regulates apoptosis and activation of platelet by activating cyclic adenosine monophosphate dependent phosphodiesterase and phosphodiesterase medicated PKA (protein kinase A), the apoptotic and activated platelet exposes phosphatidylserine, so that the phosphatidylserine is swallowed by macrophages. Inhibition or gene knockout of Akt or Akt medicated platelet activation and apoptosis or blocking of phosphatidylserine ectropion can stop clearance of antibody-bound platelet. Research indicates that the Akt inhibitor can be used for an anti-platelet membrane glycoprotein Ib alpha antibody to induce the treatment process of platelet number change related diseases and inhibit decrease of the number of platelets in peripheral circulation blood, so that the Akt inhibitor has the potential of being developed into novel platelet protection drugs and novel drugs for treating thrombocytopenic diseases and has great scientific research and economic value.

The invention relates to a series of compounds with particular activity as inhibitors of the serine-threonine kinase AKT. Also provided are pharmaceutical compositions comprising same as well as methods for treating cancer.

The invention relates to the technical field of drugs and particularly relates to a pharmaceutical composition with a synergistic effect for treating pancreatic cancer. The pharmaceutical compositioncontains adenosine and an Akt inhibitor. The pharmaceutical composition has the advantages that by utilizing a drug provided by the invention, apoptosis cascade signals in pancreatic cancer cells canbe activated, meanwhile, a mechanism that pancreatic cancer cells resist the killing of the drug through aging signals is weakened, so that the in-vivo multiplication of pancreatic cancer is inhibited; and by utilizing the Akt inhibitor, the sensitivity of pancreatic cancer to exogenous adenosine is improved, and meanwhile, relatively low drug toxicity is maintained, so that a new strategy is provided for the treatment of pancreatic cancer.

The invention relates to a series of compounds with particular activity as inhibitors of the serine-threonine kinase AKT. Also provided are pharmaceutical compositions comprising same as well as methods for treating cancer.

The present invention relates to an Akt inhibitor comprising a compound represented by formula I:wherein R is C4-30 linear or branched acyl, which may be substituted. The present invention further relates to a method of screening for a substance inhibiting acylated homoserine lactone by culturing animal cells with a test substance in the presence of acylated homoserine lactone represented by the above formula I, and then detecting inhibition of Akt activity or inhibition of the survival signalling pathway in which Akt is involved in the cells.

The invention discloses a novel method for synthesizing a key intermediate, N-substituted-1-(4-aminophenyl) cyclobutylamine (I), of a PKB / Akt inhibitor. The method comprises the steps that 1-(4-nitrophenyl) cyclobutane formonitrile (III) is obtained through nitration of 1-phenyl cyclobutane formonitrile (II), the compound (III) is hydrolyzed into 1-(4-nitrophenyl) cyclobutane formamide (IV) under the action of an oxidizing agent, the compound (IV) is subjected to rearrangement reaction to generate 1-(4-nitrophenyl) cyclobutylamine (V), the intermediate compound (V) does not need to be purified and can further react with a corresponding reagent to generate N-substituted-1-(4-nitrophenyl) cyclobutylamine (VI), and the compound (V) or (VI) reacts under the action of a reducing agent to form the compound (I). The method has the advantages of being low in cost, environmentally friendly, high in yield and the like and is suitable for industrial production.

The present invention relates to compounds of general formula I for the treatment of malignancy by inhibition of PI3-Akt pathway and or induction of NO. The present invention also relates to the use of compound of general formula I for the treatment of malignancy by inhibition of PI3-Akt pathway and or induction of NO. The present invention further relates to a method of treating malignancy by inhibition of PI3-Akt pathway and or induction of NO by administration of compound or said composition to a mammal in need thereof.

Methods and compositions are provided for inhibiting or treating a herpesvirus infection in a subject using inhibitors of mammalian Akt.

Disclosed are new members of a class of non-lipid small molecule inhibitors which interfere with the interaction between phosphoinositol-3,4,5-triphosphate (PIP3) and pleckstrin homology (PH) domains. These molecules target a broad range of PIP3-dependent signaling events in vitro and exert significant anti-tumor activity in vivo, with improved activity and selectivity toward particular PH domains. The small molecule inhibitors of the invention can be used alone or together with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or other cancer medicament to treat cancer. Small molecule inhibitors of the invention act synergistically in combination with TRAIL and with other Akt inhibitors in treating cancer. Pharmaceutical compositions and methods for treating cancer are provided.

The invention provides an application of triciribine serving as a sole effective component to preparation of a medicine for treating hepatic cancers. Indexes such as weight, hepatic weight and hepaticcoefficient can be remarkably improved by the triciribine serving as the effective component and become more normal, the number of hyperplastic nodules on a hepatic surface is remarkably decreased, the occupied area of the hepatocellular carcinoma is remarkably reduced, and a hepatic lobule structure is improved.

The present invention discloses a hepatic stellate cell targeted magnetic resonance molecular imaging agent capable of assessing liver fibrosis degree and a preparation method of the hepatic stellatecell targeted magnetic resonance molecular imaging agent, and belongs to the technical field of medicine and biological imaging. The hepatic stellate cell targeted magnetic resonance molecular imagingagent can specifically target hepatic stellate cells by coupling retinol molecules and AKT inhibitors to detect degree and development liver fibrosis process. The hepatic stellate cell targeted magnetic resonance molecular imaging agent is characterized in that the coupled retinol has a magnetic resonance imaging function, at the same time, the coupled AKT inhibitors have a function of treating liver fibrosis, and a purpose of integration of diagnosis and treatment is reached. The hepatic stellate cell targeted magnetic resonance molecular imaging agent is characterized by being high in imaging sensitivity.

The present invention relates to compounds that are useful as inhibitors of the activity of one or more isoforms of the serine / threonine kinase, AKT. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer.

A novel combination comprising a 17 α-hydroxylase / C17,20 lyase inhibitor, for example: (3β)-17-(pyridin-3-yl)androsta-5, 16-dien-3-ol or a pharmaceutically acceptable salt or ester thereof, and an AKT inhibitor, for example: N-{(1 S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide, or a pharmaceutically acceptable salt thereof, and optional additional antineoplastic agents; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of 17 α-hydroxylase / C17,20 lyase and / or AKT inhibition is beneficial, e.g., cancer.

The present invention relates to a kind of 5-thiazole amides compound and biological application, its structural formula is The present invention provides 5-thiazole amide compounds represented by general formula (I) targeting AKT / PKB kinase (ATP binding site). Experiments have proved that the thiazole amide AKT inhibitor involved in the present invention can significantly inhibit the activity of AKT kinase in vitro, and has a strong proliferation inhibitory effect on various tumor cell lines with high AKT activity, indicating that thiazole amide compounds can be used for Preparation of antitumor drugs.

Disclosed herein is a species of peptide and non-peptide inhibitors of Akt, an oncogenic protein. Beginning with a residue of Akt target substrate GSK-3, the functional domains of the GSK-3 residue were characterized. Functionally homologous non-peptide groups were substituted for the amino acids of the GSK-3 creating a hybrid peptide-non-peptide and non-peptide compounds capable of binding to Akt. The non-peptide compounds show increased stability and rigidity compared to peptide counterparts and are less susceptible to degradation. The bound non-peptide compounds exhibit an inhibitory effect on Akt, similar to peptide-based Akt inhibitors.

The invention discloses an inhibitor for a hepatoma carcinoma cell. The inhibitor for the hepatoma carcinoma cell comprises a PPAR (Peroxisome Proliferator Activated Receptor) gamma agonist and AKT inhibitor triciribine, wherein the PPAR gamma agonist is rosiglitazone or 15d-PGJ2; the mass ratio of the PPAR gamma agonist rosiglitazone to the AKT inhibitor triciribine is 100:1; and the mass mole ratio of the PPAR gamma agonist 15d-PGJ2 to the AKT inhibitor triciribine is 1g:(20-100)mu.mol. The inhibitor for the hepatoma carcinoma cell provided by the invention can effectively inhibit the initial cell subset of the HCC (Hepatocellular Carcinoma) tumor and effectively inhibit the tumor growth. A possible effective therapeutic strategy is supplied to the clinic treatment for the HCC.

The invention relates to a method of inducing Foxp3 expression in a T cell comprising(i) stimulating a T cell(ii) inhibiting signalling via PI3K alpha or PI3K delta or m-TOR or Akt in said T cell, wherein said inhibition is commenced 10 to 22 hours after the stimulation of (i). The invention also relates to certain uses of PI3K inhibitors, PI3K inhibitors for particular uses, and kits.