59 results about "Phosphatidylinositol" patented technology

This disclosure provides compounds of Formula (X), and pharmaceutically acceptable salts thereof, that reduce levels of phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3Kα), as well as methods of making and using same, and compositions comprising Formula (X), and pharmaceutically acceptable salts thereof.

The invention provides an application of a phosphatidylinositol monophosphate 5-kinase gene BnPIP5K9 of rape in regulating and controlling the oil content of the rape. The genetic basis of the oil content of rape seeds is analyzed on the basis of multiple omics, and it is found that the expression quantity of the phosphatidylinositol monophosphate 5-kinase gene BnPIP5K9 in rape is significantly positively correlated with the oil content; the gene BnPIP5K9 is subjected to gene overexpression and knockout to create a mutant for functional verification by further utilizing a tobacco mosaic virus double-35S promoter and a CRISPR / Cas9 gene editing technology, the result shows that the oil content of rape seeds can be remarkably increased by 2.16-2.77% by overexpression of the gene, in addition, rape germplasm resources with gene BnPIP5K9 function deficiency can be obtained through the CRISPR / Cas9 technology, and the rape seed quality is improved. A new theory and a new gene resource are provided for high-oil breeding and oil improvement of the rape, and the method has extremely high application value and potential.

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.

Inositol monophosphatase 1 (IMPA1) controls the activity of the primary cell proliferation signaling cascades activated through the inositol-dependent phosphorylation of Akt and PKCs. Furthermore, IMPA1 -mediated control of cell proliferation involves the recruitment of cytosolic IMPA1 on a plasma membrane by the receptor for advanced glycation endproducts (RAGE). Interaction between IMPA1 and RAGE redistributes inositols from the cytosolic pool to membrane microdomains and amplifies the synthesis of membrane-bound phosphatidylinositols (Ptdins) to trigger inositol-dependent cell proliferation. Thus, the peptide compositions described herein inhibit the formation of the complex between IMPA1 and RAGE (e.g., a pathogenic complex) to control over-proliferative cells.

This invention provides the application of phosphatidylinositol (16:0 / 18:3(9 cis, 12 cis, 15 cis)) in the identification of Hainan camellia, relating to the field of food testing technology. The phosphatidylinositol (16:0 / 18:3(9 cis, 12 cis, 15 cis)) can be used as a characteristic marker for the identification of Hainan camellia. This invention is the first to discover that the kernels of Hainan camellia contain high levels of phosphatidylinositol (16:0 / 18:3(9 cis, 12 cis, 15 cis)), while phosphatidylinositol (16:0 / 18:3(9 cis, 12 cis, 15 cis)) is not found or present in extremely low amounts in the kernels of other camellia species besides Hainan camellia. Phosphatidylinositol (16:0 / 18:3(9 cis, 12 cis, 15 cis)) can be used to identify and distinguish Hainan camellia from other camellia species. Furthermore, this identification method is simple to operate and achieves rapid, objective, and accurate identification of Hainan camellia.

The present application provides methods for preparing (R)-4-(3-((S)-1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one, which is useful as a phosphoinositide 3-kinase-delta (PI3Ks) inhibitor, as well as salt forms and intermediates related thereto.

This invention relates to the prevention and / or treatment of protein tyrosine kinase-mediated diseases, particularly phosphatidylinositol 3-kinase (PI3Ks)-mediated diseases. PI3Ks are well known as oncological targets, and several PI3K inhibitors have been developed that inhibit numerous class 1A PI3K isoforms. The development of selective inhibitors of PI3K-α may enable sufficient targeted inhibition while avoiding some of the known toxic drawbacks of pan-PI3K inhibitors. The inventors have discovered that a novel carbamoti-oil-pyrrolidine-carboxamide compound of formula (I) exhibits advantageous PI3K inhibitory activity, particularly with high selectivity for the isoform PI3K-α. In particular, this invention relates to the compound of formula (I), or deuterated or tritiated forms of the compound of formula (I), and pharmaceutically acceptable salts thereof. [Formula 1] The present invention also relates to pharmaceutical compositions containing a compound of formula (I) for use in the treatment and / or prevention of protein tyrosine kinase-mediated diseases, and to a compound of formula (I).

The invention discloses an application of glycosylated phosphatidylinositol specific phospholipase D1 (GPLD1) as a sperm-egg recognition and / or binding regulation molecule.

The invention relates to the technical field of radiopharmaceuticals, and discloses a targeted GPC3 polypeptide ligand, which has a structural general formula: C-L-P, wherein C is a chelating group; l is a linker; p is a targeted phosphatidylinositol proteoglycan-3 (GPC3) polypeptide pharmacodynamic group; the linker is a covalent linker or a reversible non-covalent linker. The invention has the following technical effects: by introducing the covalent linker or the reversible non-covalent linker, the chemical structure of the targeted GPC3 polypeptide ligand is optimized, the targeting property of the targeted GPC3 polypeptide radiopharmaceutical is improved, and the pharmacokinetic characteristics are improved; the defects that an existing targeted GPC3 polypeptide radiopharmaceutical is low in tumor uptake, short in tumor residence time, poor in pharmacokinetic characteristic and the like are overcome. The invention further discloses a targeted GPC3 polypeptide radiopharmaceutical as well as a preparation method and application of the targeted GPC3 polypeptide radiopharmaceutical.

The invention relates to pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivatives as well as a synthesis method and application thereof. The pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivatives have structural general formulas I and II. The pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivative disclosed by the invention shows remarkable inhibitory activity on phosphatidylinositol-3-kinase and histone deacetylase. The pyrazolo [3, 4-d] pyrimidine-hydroxamic acid derivative disclosed by the invention can be used as a phosphatidylinositol-3-kinase / histone deacetylase double-target inhibitor, and is used for preparing medicines for treating various malignant tumors jointly mediated by phosphatidylinositol-3-kinase and histone deacetylase.

The invention provides a stable alprostadil injection and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The stable alprostadil injection comprises the following components: alprostadil, oil for injection, a compound emulsifier, an osmotic pressure regulator and water for injection. According to the invention, a certain amount of soybean phosphatidylinositol is used as an auxiliary emulsifier, and the auxiliary emulsifier and high-purity egg yolk lecithin (for injection) form a composite emulsifier, so that the chemical stability of the product can be remarkably improved, the product can tolerate an over-killing method, the product has a high SAL (Sterile Assurance Language), and the product can be stored for 24 months at a conventional cold chain temperature (2-8 DEG C), and the product quality still meets the national drug standard.

The invention relates to a big data screening method of a traditional Chinese medicine compound for treating enteritis and application thereof, and belongs to the field of traditional Chinese medicine screening based on a data mining technology, animal experiment efficacy investigation and network pharmacology prediction. Comprising the following steps: performing data arrangement specification on a traditional Chinese medicine compound for treating enteritis based on a data mining technology; analyzing and summarizing the standardized data to obtain a new traditional Chinese medicine compound (AEND); constructing an acute enteritis mouse model, and performing pharmacodynamic evaluation on the traditional Chinese medicine compound; predicting the action mechanism of the screened traditional Chinese medicine compound based on a network pharmacology method; a molecular docking technology is applied to virtually verify the action target of the traditional Chinese medicine compound on acute enteritis; the pathway protein of a mammalian cell receptor tyrosine kinase mediated phosphatidylinositol related (PI3K / AKT) signal pathway is detected. According to the invention, a new formula AEND is screened out based on data mining, and a pharmacological experiment verifies that the AEND has a protective effect on mice with acute enteritis. The developed traditional Chinese medicine compound has the effects of resisting inflammation and regulating the homeostasis of intestinal flora.

A medium for Bacillus cereus group detection, which is favorable in growth of Bacillus cereus regardless of the temperature condition, and further is excellent in selectivity; and a method for detecting a Bacillus cereus group using the medium. The medium for Bacillus cereus group detection includes a phosphatidylinositol-specific phospholipase C substrate having a detectable chromogenic or fluorescent free radical; and trimethoprim. The medium further includes a β-lactam antibiotic. The medium further includes an antifungal agent. The method for detecting further includes inoculating a sample into the medium to culture the sample; and determining a detectable colony on the medium.

The present technology relates to the field of cancer treatment. In particular, the present technology relates to polypeptides targeting phosphatidylinositolprotein-3 (GPC3) and T cell receptor (TCR) for use in the treatment of phosphatidylinositolprotein-3 positive (GPC3 +) solid tumors, such as hepatocellular carcinoma (HCC) or non-small cell lung cancer (NSCLC). In addition, the technology relates to the dosage of said polypeptide when used as therapy.

The present disclosure relates to the use of inhibitors of phosphoinositide 3-kinase (PI3K) that target the allosteric and orthosteric pockets of PI3K in methods for treating, preventing, or ameliorating diseases or disorders in which PI3K plays a role (or for use in treating, preventing, or ameliorating diseases or disorders). PI3K inhibitors may be utilized in combination and may target the allosteric or orthosteric pockets of PI3K α simultaneously, separately, or sequentially. In some aspects of the disclosed methods, the PI3K α inhibitor may target the allosteric or orthosteric pocket of a PI3K α mutant that is resistant to treatment with another PI3K α inhibitor that targets a different pocket of PI3K α.

The application discloses a method for regulating virus proliferation in rice planthopper. The method regulates the content of 3,5-bisphospho phosphatidylinositol (PI(3,5)P2) to regulate the proliferation of rice black-streaked dwarf virus in the body of Laodelphax striatellus and southern rice black-streaked dwarf virus in the body of white-backed planthopper. The PI(3,5)P2 inhibitor or dsRNA of PI(3,5)P2 synthesis enzyme gene PIKfyve is applied by microinjection, drop or spraying to reduce the content of PI(3,5)P2 in the body of Laodelphax striatellus and white-backed planthopper, thereby inhibiting the proliferation of rice black-streaked dwarf virus in the body of Laodelphax striatellus and southern rice black-streaked dwarf virus in the body of white-backed planthopper. The PI(3,5)P2 homolog PI(3,5)P2-diC8 is applied to Laodelphax striatellus to increase the content of PI(3,5)P2, thereby promoting the proliferation of rice black-streaked dwarf virus in the body of Laodelphax striatellus. The application provides a new method for controlling virus diseases transmitted by vector insects.

This invention relates to 2-amino-4-methylquinazoline compounds, their preparation methods, uses, and pharmaceutical compositions. Specifically, it provides a compound represented by Formula I, which is a phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor that can be used to prevent and / or treat diseases related to PI3Kδ activity, such as tumors, autoimmune diseases, immunodeficiency diseases, inflammation, kidney diseases, cardiovascular diseases, metabolic / endocrine disorders, or neurological diseases.

The invention relates to quinazoline compounds, the preparation method, use, and the pharmaceutical composition thereof. The said quinazoline compounds, which are represented by Formula (I), are phosphatidylinositol 3-kinase (PI3K) inhibitors, and can be applied to prevent and / or treat PI3K activity-related diseases, such as cancer, immune diseases, cardiovascular diseases, viral infections, inflammation, metabolism / endocrine function disorders or neurological diseases.

The strain BS-14 can convert the nutrients in the solid culture into nutrients absorbed and utilized by the bacillus subtilis, and the microenvironment generated by the fermentation of the strain BS-14 is also beneficial to promote the fermentation of MQ013-26, so that the enzyme activity concentration of the natto kinase is further improved. The strain BS-14 can further decompose phospholipid substances (phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol) and fat, so that the spoilage odor of the freeze-dried powder can be further improved, and the shelf life can be prolonged. The strain BS-14 can further generate active peptides against pathogenic microorganisms, and has significant bacteriostatic activity, so that the quality safety of the freeze-dried powder is improved.

The disclosure provides phosphatidylinositol 4-kinase beta inhibitor compositions and their uses in treating diseases caused or exacerbated by human rhinovirus infection.

The invention discloses a biomarker for predicting the effect of improving blood glucose through diet intervention of a type 2 diabetes patient and application of the biomarker. The biomarker is composed of the following metabolite markers: 16 [alpha]-hydroxy dehydroepiandrostene-3-sulfate, 1-palmitoyl-2-linoleyl phosphatidylinositol glycerol (16: 0 / 18: 2), 1-oleoyl-2-arachidonyl phosphatidyl ethanolamine (18: 1 / 20: 4), 3-methoxy tyrosine and methyl succinyl carnitine, and the pH value of the biomarker is 7-8. The method is used for predicting the blood glucose improving effect of diet intervention of the type 2 diabetes patients, the prediction efficiency of traditional clinical indexes can be remarkably improved, the success rate of long-term blood glucose control is increased, accordingly, the treatment efficiency is improved, and application of precise medicine in type 2 diabetes management is achieved.

This disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, and compounds of Formula (II), and pharmaceutically acceptable salts thereof, that inhibit phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3Kα). These chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) PI3Kα activation contributes to the pathology and / or symptoms and / or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing the same as well as methods of using and making the same.

The invention provides application of an STG5.2 gene in regulating and controlling salt tolerance of rice, and relates to the technical field of biology. According to the invention, rice LOCOs05g07260 (STG5.2, Salt Toolance and Grain Yield-Related Gene 5.2) is obtained through cloning, the rice LOCOs05g07260 is annotated as a phosphatidylinositol glycosylation related gene, the research of the inventor finds that the STG5.2 gene has the function of positively regulating and controlling the salt tolerance and the grain yield of rice, and after the gene is knocked out, the growth of a plant is hindered in a saline-alkaline stress and the grain yield is severely reduced. The invention has potential application value for excavating the rice salt-tolerant gene and cultivating a new salt-tolerant rice variety.

The present disclosure provides a process for the preparation of compounds of formula (I), such as (R)-1-(2-aminopyrimidin-5-yl)-3-(1-(5, 7-difluoro-3-methylbenzofuran-2-yl)-2, 2, 2-trifluoroethyl) urea (Compound 1), and salts and / or solvates thereof, that inhibit the phosphatidylinositol 4, 5-diphosphate 3-kinase (PI3K) subtype alpha (PI3K alpha).

This application relates to the field of tumor immunodiagnostic technology, and particularly to a monoclonal antibody, polynucleotide, preparation method, and application of antiphosphatidylinositol proteoglycan-3; the monoclonal antibody includes a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region includes heavy chain region CDR1 with amino acid sequence as shown in SEQ ID NO:1, heavy chain region CDR2 with amino acid sequence as shown in SEQ ID NO:2, and heavy chain region CDR3 with amino acid sequence as shown in SEQ ID NO:3; the light chain variable region includes light chain region CDR1 with amino acid sequence as shown in SEQ ID NO:4, light chain region CDR2 with amino acid sequence as shown in SEQ ID NO:5, and light chain region CDR3 with amino acid sequence as shown in SEQ ID NO:6; the dissociation constant KD(M) of the monoclonal antibody against GPC3 antigen is 1.21E-11, which is a high-affinity N-terminal antibody, suitable for the detection of GPC3 in clinical serum samples.

A method for diagnosing facioscapulohumeral muscular dystrophy (FSHD) using one or more biomarkers is provided. More particularly, provided is a method for diagnosing FSHD in a subject, the method comprising detecting the presence of a biomarker or change in level of a biomarker in a biological sample from the subject, wherein the biomarker is wherein the biomarker is mannose binding lectin 2 (MBL2), junction plakoglobin (JUP), desmoplakin (DSP), tetranectin (CLEC3B), complement component 7 (C7), complement component 9 (C9), tenascin C (TNG), lumican (LUM), phosphatidylinositol-glycan-specific phospholipase D (GPLD1 ), complement component 4 binding protein, beta chain (C4BPB), carnosine dipeptidase (CNDP1), or immunoglobulin kappa variable 2-30 (IGKV2-30), or a combination of any two or more of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, LUM, GPLD1, C4BPB, CNDP1, or IGKV2-30. In some aspects, when the change in level of the biomarker is an increase in the level of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, and / or LUM, or a combination of any thereof, the subject is diagnosed as having FSHD. In some aspects, when the change in level of the biomarker is a decrease in the level of GPLD1, C4BPB, CNDP1, and / or IGKV2-30, or a combination of any thereof, the subject is diagnosed as having FSHD. Also provided is a method for determining efficacy of a therapeutic treatment for FSHD in a subject, the method comprising measuring the level of a biomarker in a biological sample from the subject before and after the treatment, and determining that the treatment is effective in treating FSHD if the level of the biomarker is decreased or increased relative to a reference level or to the level of the biomarker in the sample from the subject before treatment, wherein when the biomarker is mannose binding lectin 2 (MBL2), junction plakoglobin (JUP), desmoplakin (DSP), tetranectin (CLEC3B), complement component 7 (C7), complement component 9 (C9), tenascin C (TNG), or lumican (LUM), or a combination of any two or more of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, or LUM, the treatment is effective when the level of the biomarker decreases, or wherein when the biomarker is phosphatidylinositol-glycan-specific phospholipase D (GPLD1), complement component 4 binding protein, beta chain (C4BPB), carnosine dipeptidase (CNDP1), or immunoglobulin kappa variable 2-30 (IGKV2-30), or a combination of any two or more of GPLD1, C4BPB, CNDP1, or IGKV2-30, the treatment is effective when the level of the biomarker increases. In various aspects, the method further comprises treating the subject diagnosed with FSHD.

The invention provides an engineered GPI anchoring signal peptide as well as a fusion protein and application thereof. Specifically, the invention provides an engineered glycosylated phosphatidylinositol (GPI) anchoring signal peptide, and compared with an original natural GPI anchoring signal peptide, the N-terminal histidine of the engineered GPI anchoring signal peptide is replaced with an uncharged non-polar amino acid of which the side chain is C3-C6 straight chain or branched chain alkyl, and the side chain of the GPI anchoring signal peptide is replaced with an uncharged non-polar amino acid of which the side chain is C3-C6 straight chain or branched chain alkyl. And comprises a flexible hydrophobic amino acid combination at its C-terminus. The invention further provides a protein molecule which comprises a functional peptide fragment connected with the GPI anchoring signal peptide engineered and modified by the invention. The GPI anchoring signal peptide disclosed by the invention has an enhanced anchoring effect, can be connected with various functional peptide fragments and can be anchored to the surface of a cell membrane in a large amount and enduringly, so that the GPI anchoring signal peptide has a wide application prospect.

Disclosed herein are crystalline forms of a phosphatidylinositol 4, 5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3K alpha) inhibitor, and formulations and uses thereof.

The present invention provides radiopharmaceuticals and conjugates targeting GPC3 as well as compositions and uses thereof. In one aspect, provided herein are conjugates comprising a peptide having affinity for GPC3 and a metal chelating agent configured to bind to a radionuclide. The conjugates described herein may further comprise a linker linking the chelating agent and the peptide. The conjugates described herein may further comprise radionuclides. In one aspect, provided herein is a radiopharmaceutical comprising a peptide and a metal chelating agent that binds to a radionuclide. The conjugates described herein may further comprise a linker linking the chelating agent and the peptide. Further provided herein are methods of treating cancer by administering the described radiopharmaceuticals, conjugates, compositions thereof.

A method of preventing or treating or controlling a respiratory disease in a bovine by delivering to a lung or trachea of the bovine a composition including a polyplex having one or more mRNA encoded with a molecule selected from lycosylphosphatidylinositol (GPI) complex, antibody immunoglobulin G (IgG), antibody immunoglobulin A (IgA), antibody immunoglobulin M (IgM), antimicrobial peptide Bactenecin 5 (Bac5), antimicrobial peptide Bactenecin 7 (Bac7), bovine myeloid antimicrobial peptide (BMAP-28), lipoxin inducing enzymes, resolvin inducing enzymes, cytokines, CRISPR associated protein 13 (Cas13) enzymes, nanoluciferase (NLuc) proteins, and gene activator, catalytically dead CRISPR-associated protein 9 fused to an activator selected from the group consisting of VP64-p65-Rta transactivation domain (dCas9-VPR), VP64, and VP64-p65-HSF1 on the N terminus and SS18 on the C-terminus, and a polymer prepared by polymerizing a diacrylate monomer; one or more linker monomers; and one or more branching monomers; and end-capping the polymer.