123 results about "Phosphatidylinositol" patented technology

Disclosed herein are crystalline forms of phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3Kα) inhibitors, and formulations and uses of same.

The present disclosure provides amino acid sequences (e.g., antibodies) capable of binding to glypican 3 protein (GPC3). The present disclosure relates to antigen binding fragments of GPC3 antibodies; conjugates of a GPC3 antibody, including an immunoconjugate; bispecific antibodies comprising a GPC3 antibody and related compositions and formulations. The disclosure also relates to methods of treating GPC3-related diseases, disorders and conditions, including cell proliferative diseases, such as cancer, more particularly liver cancer, using these sequences, such as GPC3 antibodies and antigen-binding fragments thereof.

The invention discloses injectable piezoelectric conductive hydrogel as well as a preparation method and application thereof, and the injectable piezoelectric conductive hydrogel is prepared by forming space coordination between piezoelectric nano-particles and conductive hydrogel through metal and a framework and uniformly fixing the piezoelectric nano-particles in the space structure of the conductive hydrogel. When the injectable piezoelectric conductive hydrogel is injected to the wound surface of a mouse wound, the hydrogel can be completely attached to the wound according to the irregular wound to form gel, and the gel is tightly attached to the wound. When a mouse moves, the piezoelectric nanoparticles are extruded to generate voltage and current, and the current is transmitted to the surface and wound of the hydrogel through the conductive hydrogel skeleton. Under the stimulation of micro-current, phosphorylation of phosphatidylinositol 3-kinase of fibroblasts is activated, then phosphorylation of protein kinase B is activated, migration and proliferation of the fibroblasts are induced, and wound healing is promoted.

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.

The invention discloses a calcium liposome for promoting bone health as well as a preparation method and application thereof. The calcium liposome is prepared from the following components in parts by weight: 3 to 7 parts of phospholipid composition, 0.1 to 0.35 part of phytosterol, 1 to 5 parts of insoluble calcium, 1 to 7.5 parts of protein and 0.1 to 1 part of modifier, wherein the phospholipid composition consists of egg yolk lecithin, phosphatidylinositol and distearoyl phosphatidylcholine, and the mass ratio of the egg yolk lecithin to the phosphatidylinositol to the distearoyl phosphatidylcholine is (8-12): (7-11): ( The specific phospholipid composition obtained through screening is combined with phytosterol to serve as a membrane material to wrap a compound of insoluble calcium and protein, so that the dispersity and the stability of the prepared calcium liposome are obviously improved, when the calcium liposome is applied to preparation of calcium soft capsules, the oil leakage phenomenon is obviously reduced, meanwhile, the absorption of an organism to calcium is also enhanced, and the bioavailability of the calcium soft capsules is improved. Particularly, the bone mineral density and the bone calcium content of an organism are obviously increased, healthy development of bones is promoted, and the difficulty and the pain point of insoluble calcium applied to the fields of functional foods, health care products, biological medicines and the like are effectively solved.

Conjugates comprising a fibroblast activation protein α (FAP-α)-targeted ligand, a bifunctional or trifunctional linker, and a phosphatidylinositol-3-kinase (PI3k) inhibitor; uses of the conjugates in the manufacture of a medicament for inhibiting progression of fibrosis in a subject; and a method of use in inhibiting progression of fibrosis in a subject.

Provided herein are methods and materials for using organisms (e.g., engineered yeast strain-derived) to generate lipid compositions which can modulate cellular aging, extend lifespan, and / or modulate gut homeostasis in a subject. The lipid compositions contain at least twelve of the lipids selected from a phosphatidylethanolamine (PE); a lysophosphatidylethanolamine (LPE); a diacylglycerol (DG); a monoglyceride (MG); an acyl carnitine (AcCa); a phosphatidic acid (PA); a phosphatidylglycerol (PG); a lysophosphatidylcholine (LPC); a triacylglycerol (TG); a cholesterol ester (ChE); a wax ester (WE); a phosphatidylserine (PS); a phosphatidylcholine (PC); a phosphatidylinositol (PI); a ceramide (Cer); and a lysophosphatidylserine (LPS).

This disclosure provides processes of preparing 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 phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3Kα).

This disclosure provides compounds of Formula (I) and pharmaceutically acceptable salts thereof, that inhibit phosphatidylinositol 4,5-bisphosphate 3 kinase (PI3K) isoform alpha (PI3Kα). These compounds are useful for treating a disease in which increased PI3Kα activation contributes to the pathology, symptoms, and / or progression of the disease (e.g., cancer) in a subject.

The present invention relates to a (4R)-sulfonylamino-L-prolinamide compound having a general structure and a pharmaceutically acceptable salt or solvate thereof. The present invention also provides a method for preparing a (4R)-sulfonylamino-L-prolinamide compound and a pharmaceutically acceptable salt or solvate thereof. The present invention further provides the use of a (4R)-sulfonylamino-L-prolinamide compound and a pharmaceutically acceptable salt or solvate thereof in the preparation of a medicament for treating a disease by inhibiting phosphatidylinositol 3-kinase α (PI3Kα). The present invention further provides a drug combination comprising a (4R)-sulfonylamino-L-prolinamide compound and a pharmaceutically acceptable salt or solvate thereof. The (4R)-sulfonylamino-L-prolinamide derivative according to the present invention has favorable pharmacological properties, for example, they can inhibit PI3Kα, and are superior to Alpelisib in activity and selectivity for PI3Kα.

Compounds and methods are provided for inhibiting a PI4-kinase. Methods of treating a pathogen infection and methods of treating cancer are also provided. The PI4-kinase inhibitor can be a compound that is a 5-aryl or heteroaryl-thiazole, e.g., as described herein. In certain embodiments, the PI4-kinase inhibitor is a substituted 2-amino-5-phenylthiazole or substituted 2-amino-5-pyridylthiazole compound. In some embodiments, the compounds have broad spectrum anti-infective activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of treating a subject for cancer using a PI4-kinase inhibitor. Aspects of the methods include inhibiting PI4-kinase in a cancer cell to reduce cellular proliferation.

The present invention provides a kind of composition containing bird's nest acid, phospholipid and polyunsaturated fatty acid and preparation method thereof, composition, when not adding any additives, bird's nest acid is dispersed in DHA grease in functional ingredients, while solving the problem that DHA is easily oxidized, promotes brain development, regulates immunity, promotes the absorption and utilization of minerals in the intestine and the effects of beauty and skin care. Phospholipids can prevent the sedimentation of bird's nest acid in ω 3 polyunsaturated fatty acid grease, and are phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol or phosphatidylserine. Not only can the sedimentation of bird's nest acid be prevented, but also the growth of nerve cells can be supported, thereby improving the absorption rate of DHA in the brain. Especially PS, itself can not only nourish the brain, enhance brain function, but also relieve mental stress and improve cognition, and is called "brain nutrient".

Disclosed herein are crystalline forms of phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) isoform alpha (PI3Kα) inhibitors, and formulations and uses of same.

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.

The invention belongs to the technical field of biotechnology, and discloses a peanut peptide for promoting cell development, which is characterized in that the sequence of the peanut peptide is Met Ala Ser Val Thr Gly Pro Ser Ser Ala Leu Ala Asp Ser Ile Gly, through the accurately designed amino acid sequence, the peanut peptide constructs a molecular level adaptation mechanism with a cell surface receptor, triggers a cascade reaction of a key signal channel of phosphatidylinositol-3 kinase PI3K, and can promote cell development. The activation effect not only accelerates the process of a cell cycle and increases the proportion of DNA synthetic cells in an S phase by 40% or more, but also directionally induces the mesenchymal stem cells to differentiate into functional cells such as muscle cells and nerve cells by up-regulating transcription factors MyoD and NeuroD1, in a three-dimensional cell culture model, the cell migration rate of an experimental group added with 200 [mu] g / mL peanut peptide is increased by 58% compared with a control group, and the cell migration rate of the experimental group added with 200 [mu] g / mL peanut peptide is increased by 30% or more compared with that of the control group. The branch density of the formed vascular-like network is increased by 3 times, and meanwhile, the test further proves that the peanut peptide has the function of promoting cell development and shows remarkable optimization capability on a tissue regeneration microenvironment.

Disclosed herein are polypeptide fragments and polynucleotides based on mutant capicua transcriptional repressor (CIC), catenin beta 1 (CTNNB1), v-erb-b2 erythroblastic leukemia viral oncogene homolog B (ERBB2), kirsten rat sarcoma (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), splicing factor 3b subunit 1 (SF3B1), SRY-box transcription factor 17 (SOX17), tumor protein 53 (TP53), and cytomegalovirus (CMV) sequences, vectors, host cells, viruses, methods for generating CD8+ T-cells, and methods of treatment. Also disclosed herein are T-cell receptors (TCRs), polynucleotides, vectors and cells comprising the TCRs, and methods of treatment.

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.

A method of treating a blood cancer comprising the administration of therapeutically effective amounts of a phosphatidylinositol 3-kinase gamma (PI3Kg) inhibitor and an antimetabolite, optionally also a therapeutically effective amount of a BCL-2 inhibitor, to a patient in need thereof. A method of identifying a blood cancer patient susceptible to treatment with a PI3Kg inhibitor. A method of treating a blood cancer comprising administration of a therapeutically effective amount of a p-21-activated kinase 1 (PAK-1) inhibitor, optionally also a therapeutically effective amount of a BCL-2 inhibitor, to a patient in need thereof.

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 discloses an oocyte culture solution and application thereof, and relates to the technical field of biological medicine, and the oocyte culture solution comprises phosphatidylinositol, L-carnitine, a bicarbonate buffer solution, an energy metabolism substrate, polyvinyl alcohol, hormone and growth factors. The oocyte culture solution is beneficial to improving the steady state unbalance phenomenon of oocyte lipid metabolism, the cytoplasm fragment rate and the cleavage fragment rate in the aging process of oocytes after ovulation are reduced, and the effect of relieving aging of the oocytes after ovulation is achieved.

We describe an antibody or antigen binding fragment thereof comprising a cloned heavy chain variable region (VH) sequence and a light chain variable region (VL) sequence selected from the group consisting of 5C4, 4H1, 1D2, 1C4, 2B5, 1F1, 1H1, 4A5, 1D8, 1D3, 2F1, 3C6, 3D12, 3A9, 1F4, 1H10, 3C12, 4G11, 4A12, 1A12, 3G12, 4F9, 4G4 and 1E1, said antibody or antigen binding fragment thereof being capable of binding specifically to glypican-3 (GPC-3) (Genbank accession number: NP004475.1), or a sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity thereto.

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.

The present disclosure provides dual functioning compounds, compositions, formulations, and methods for inducing or modulating an immune or inflammatory response and treating diseases or disorders (e.g., cancer, autoimmune diseases, inflammatory diseases, and infectious diseases) with the compounds or compositions thereof. In particular disclosed herein are dual functioning compounds comprising a stimulator of interferon (IFN) genes (STING) agonist moiety and a second active moiety selected from an indoleamine 2,3-dioxygenase (IDO) inhibitor and phosphatidylinositol 3-kinase (PI3K) inhibitor, and compositions and formulations thereof.