30 results about "Akt phosphorylation" patented technology

Disclosed are peptides having SEQ ID NOs: 1 to 24 that induce superoxide generation by human monocytes or neutrophils; that induce an intracellular calcium increase by human peripheral blood monocytes or neutrophils; binds to formyl peptide receptor or formyl peptide receptor-like 1; that induce chemotactic migration of human monocytes or neutrophils in vitro; that induce degranulation in formyl peptide receptor expressing cells or formyl peptide receptor-like 1 expressing cells; that stimulate extracellular signal regulated protein kinase phosphorylation via activation of formyl peptide receptor or formyl peptide receptor-like 1; or that stimulate Akt phosphorylation via activation of formyl peptide receptor or formyl peptide receptor-like 1.

The present invention relates generally to PHLPP, a novel phosphatase that inactivates Akt (protein kinase B) by directly dephosphorylating the hydrophobic domain of the C-terminus. More specifically, the invention relates to PHLPP polynucleotides and the polypeptides encoded by these polynucleotides and the use of these polynucleotides and polypeptides in the treatment and diagnosis of biological conditions mediated by Akt phosphorylation, particularly cancer. This invention relates to PHLPP polynucleotides and polypeptides as well as vectors, host cells, antibodies directed to PHLPP polynucleotides and polypeptides and recombinant and synthetic methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of PHLPP polynucleotides and polypeptides of the invention.

The present invention relates to uses of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, analogues and derivatives thereof, for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The present invention further provides a method for assessing responsiveness to treatment with the peptide of the invention. In addition, the present invention relates to prognosis of ALS progression, using Akt and phosphorylated Akt as biomarkers.

The invention provides compositions and methods that modulate the activity of AKT family kinase proteins, including AKT1, AKT2 and AKT3 (also referred to as PKBα, PKBβand PKBγ). Specifically, the invention provides a number of phenoxazine and acridone compounds that inhibit AKT phosphorylation and kinase activity. The invention provides compositions for and methods of modulating AKT activity, inhibiting cell growth, treating cancer, treating transplant rejection, and treating coronary artery disease based upon the phenoxazine and acridone compounds of the invention.

Oxygen toxicity is one of the major risk factors in the development of the chronic lung disease or bronchopulmonary dysplasia in premature infants. Using proteomic analysis, we discovered mitochondrial aldehyde dehydrogenase (mtALDH or ALDH2) was down-regulated in neonatal rat lung after hyperoxic exposure. To study the role of mtALDH in hyperoxic lung injury, we overexpressed mtALDH in human lung epithelial cells (A549) and found that mtALDH significantly reduced hyperoxia-induced cell death. Compared to control cells (Neo-A549), the necrotic cell death in mtALDH overexpressing cells (mtALDH-A549) decreased from 25.3% to 6.5%, 50.5% to 9.1% and 52.4% to 15.06% after 24-, 48- and 72-hour hyperoxic exposure, respectively. The levels of intracellular and mitochondria-derived reactive oxygen species (ROS) in mtALDH-A549 cells after hyperoxic exposure were significantly lowered compared to Neo-A549 cells. mtALDH overexpression significantly stimulated extracellular signal regulated kinase (ERK) phosphorylation under normoxic and hyperoxic conditions. Inhibition of ERK phosphorylation partially eliminated the protective effect of mtALDH in hyperoxia-induced cell death, suggesting ERK activation by mtALDH conferred cellular resistance to hyperoxia. mtALDH overexpression augmented Akt phosphorylation and maintained the total Akt level in mtALDH-A549 cells under normoxic and hyperoxic conditions. Inhibition of PI3K activation by LY294002 in mtALDH-A549 cells significantly increased necrotic cell death after hyperoxic exposure, indicating that PI3K/Akt activation by mtALDH played an important role in cell survival after hyperoxia. Taken together, these data demonstrate that mtALDH overexpression attenuates hyperoxia-induced cell death in lung epithelial cells through reduction of ROS, activation of ERK/MAPK and PI3K/Akt cell survival signaling pathways.

The invention discloses a composition for inhibiting glioma growth and an application thereof. The composition comprises a substance for improving the expression of protein (PTEN) as shown in sequence 1 of the sequence table, and a substance for inhibiting the expression of protein (B) as shown in sequence 3 of the sequence table. Experiments demonstrate that when the combination of recovering the expression of protein PTEN with inhibiting the expression of protein B is compared with only recovery of the expression of protein PTEN or only inhibition of expression of protein B, the AKT phosphorylation level of recombinant glioma cell lines is significantly decreased, cell proliferation and colony formation are significantly inhibited, and the proportion of cells stopping at the G0/G1 phase and the cell apoptosis rate are significantly increased; Glioma in transplanted mouse body has no increase in size at 20-48 days after treatment by recovering the expression of protein PTEN combined with inhibiting the expression of protein B, and the tumor weight is almost zero at the 48th day after the treatment. The invention provides a new and effective combination therapy scheme for glioma, and has wide application prospects.

The invention provides methods and materials for identifying agents for preventing and/or treating anthrax and similar diseases. Embodiments provide strains and model systems for studying non-lethal and lethal exposure to anthrax and similar disease vectors. Embodiments provide materials and methods for using the strains and model systems for differential profiling, such as proteomic profiling, such as differentiation phosphorylation profiling, to target identification and therapeutics discovery and development. Embodiments provide pharmaceutically acceptable compositions, and methods for using them to prevent and/or treat anthrax and similar diseases comprising an agent that decreases the activity of caspase ¼, such as YVAD, and/or an agent that increases the phosphorylation of AKT, such as IB-MECA or Cl-IB-MECA, together with, in particular embodiments, an antibiotic, such as ciprofloxacin. Kits comprising the same are provided as well, among other things.

Provided are methods for protecting against or reducing neurotoxicity of exposure to a neurotoxic agent, comprising administering an electrokinetically altered aqueous fluid as provided herein in an amount sufficient to provide for neuroprotection against the neurotoxic agent, preferably where protecting against or reducing loss of motor coordination in the subject exposed to the neurotoxin is afforded. In certain aspects, protecting or reducing neurotoxin-mediated neuronal apoptosis is afforded, and/or activating or inducing at least one of PI-3 kinase and Akt phosphorylation in neurons is afforded. Preferably, administering the fluid comprises administering the fluid prior to exposure to the neurotoxic agent. Additionally provided are methods for preserving or improving motor coordination in a subject having a neurodegenerative condition or disease, comprising administering an electrokinetically altered aqueous fluid as provided herein in an amount sufficient to provide for preserving or improving motor coordination in the subject.

A peptide comprising an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, according to the present invention, shows proliferation and differentiation promotion of osteoblast and proliferation and activation promotion of periodontal ligament fibroblast. A peptide, according to the present invention, increases BMP signaling such as SMAD1/5/8 phosphorylation and increases the growth of osteoblast and the expression of a differentiation marker such as COL1A1, BSP and ALP, thereby ultimately showing osteoblast activation. A peptide, according to the present invention, promotes the growth of periodontal ligament fibroblast by means of PI3K and Akt phosphorylation and increases the expression of an activation marker such as COL1A1 and DSPP, thereby ultimately showing periodontal tissue regeneration activation. Provided are a composition for preventing or treating bone diseases and a composition for preventing or treating periodontal diseases, the compositions comprising the aforementioned peptide.

Disclosed are a use of a methylacryloyl benzimidazolone derivative, an optical isomer or a pharmaceutically acceptable salt or prodrug thereof in the preparation of: (a) a pharmaceutical composition or reagent for down-regulating the activity of PI3K/Akt pathways; (b) a pharmaceutical composition or reagent for treating or inhibiting a tumour; and/or inhibiting tumour cell growth; and/or (c) a pharmaceutical composition or reagent for blocking the cell cycle. The compounds involved in the present invention can down-regulate the level of Akt phosphorylation in P 13K/Akt signaling pathways, and the functional effects of the compounds are equivalent to those of a novel small-molecular targeting drug MK2206; while the research at the cellular level has found that the methylacryloyl benzimidazolone derivatives represented by FD1 have a good proliferation inhibiting effect on tumour cells. What is different from MK2206 is that FD1 has better effects on a PTEN deleted cell.

The invention discloses a wortmannin prodrug as well as preparation and application thereof. Inhibitors with different sustained release effects are constructed by using wortmannin as matrix and adopting a simple chemical synthesis means. The inhibitors provided by the invention are verified to still maintain the impact effect on a PI3K pathway by means of an in-vitro slow release test, a cancer cell proliferation test and AKT phosphorylation detection, and anti-tumor targeting is improved by utilizing drug slow release and a biotin targeting effect, so that dosage for inhibition of cancer cell proliferation is greatly reduced.

The invention relates to the technical field of medicines, in particular to application of chlorpromazine hydrochloride to treatment of endometrial cancer, and the endometrial cancer comprises type I endometrial cancer and type II endometrial cancer. Experiments find that chlorpromazine hydrochloride has an inhibiting effect on proliferation, clone formation and migration ability of endometrial cancer Ishikawa (ISK cells) and KLE cells, can induce apoptosis, up-regulate cell PRB expression, inhibit cell AKT phosphorylation and inhibit growth of subcutaneous transplantation tumors of mice, and is proved to be effective in mouse experiments. Therefore, the invention provides a new application of the antipsychotic drug chlorpromazine hydrochloride in treatment of endometrial cancer.

Provided is a method for suppressing diabetes and/or hepatic lipids in a mammal to lower blood glucose levels and hepatic total lipids and triacylglycerol contents by increasing AMP-activated protein kinase (AMPK) phosphorylation in both skeletal muscle and liver tissue, and Akt phosphorylation and membraneprotein levels of glucose transporter 4 (GLUT4) in skeletal muscle. The method comprises administrating to the mammal an effective amount of tormentic acid or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

The invention discloses a nuclear transcription factor mutant rFoxO3a-MTSS as well as a recombinant vector and application thereof. The nuclear transcription factor mutant rFoxO3a-MTSS is obtained by replacing the 32nd threonine, the 252nd serine and the 314th serine in a wild type rat FoxO3a peptide chain into alanine simultaneously, wherein the amino acid sequence of the mutant rFoxO3a-MTSS is shown in the SEQ ID NO.1; the sequence of nucleotide coding the mutant is shown in the SEQ ID NO.2. Compared with a wild type rFoxO3a, the mutant rFoxO3a-MTSS discloses by the invention has the characteristic of capable of avoiding phosphorylation by an upstream regulatory factor Akt, can keep in a continuous active state in vivo, and has important scientific significance and potential application value on research on functions of FoxO3a genes and targeted therapy of diseases related to the FoxO3a genes.

A peptide comprising an amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, according to the present invention, shows proliferation and differentiation promotion of osteoblast and proliferation and activation promotion of periodontal ligament fibroblast. A peptide, according to the present invention, increases BMP signaling such as SMAD1/5/8 phosphorylation and increases the growth of osteoblast and the expression of a differentiation marker such as COL1A1, BSP and ALP, thereby ultimately showing osteoblast activation. A peptide, according to the present invention, promotes the growth of periodontal ligament fibroblast by means of PI3K and Akt phosphorylation and increases the expression of an activation marker such as COL1A1 and DSPP, thereby ultimately showing periodontal tissue regeneration activation. Provided are a composition for preventing or treating bone diseases and a composition for preventing or treating periodontal diseases, the compositions comprising the aforementioned peptide.

The invention discloses application of a calycosin derivative in preparing a medicine for treating cerebral ischemia reperfusion injury. Through experiments, an applicant discovers that the calycosin derivative can up-regulate expression levels of ERalpha and GPR30, and can be more beneficial to reducing a neurological function score, reducing a cerebral infarction volume and reducing a cerebral oedema degree compared with calycosin; the calycosin derivative can dose-dependently up-regulate an ERK1/2 and Akt phosphorylation level, and plays a role in protecting an ischemia reperfusion injury nerve cell. The calycosin derivative has a structure as shown in the formula (I) which is shown in the description.