55 results about "Cholesterol acyltransferase" patented technology

The invention relates to methods for administering inhibitors of acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity, and for treating Alzheimer's disease, atherosclerosis, and other ACAT-related diseases. The invention also relates to sustained release delivery systems.

The present invention relates to the field of medical technology, and in particular relates to a category of novel sulphonyl substituted xanthene ketone compounds that have a structural formula as shown in the right, a preparation method and application thereof. The compound has high inhibitory activity for ACAT1 / ACAT2; most of the compounds have high inhibitory activity for acyl coenzyme A cholesterol acyltransferase (ACAT). The compounds can be used for preparing anti-atherosclerosis drug combination. Furthermore, the compounds can be used as a preventive or a treating agent of such diseases as angina, myocardial infarction, cerebral infarction, apoplexy, Alzheimer's disease, acute coronary syndrome, PTCA or restenosis of coronary artery after a bracket is arranged. The compounds can be used as a treating agent to adjust the function of sebaceous glands of the skin and inhibit the excessive generation of sebum. And the compounds can be used for treating such diseases as acne-like damage caused by oily skin, acne, seborrhea and corticosteroids.

The present invention offers novel cyclic diamine compounds and a pharmaceutical composition containing the same.The present invention relates to a compound represented by the formula (I) or salt(s) or solvate(s) thereof. (In the formula, is an optionally substituted divalent residue of benzene, pyridine, cyclohexane or naphthalene or is a vinylene group whereAr is an optionally substituted aryl group;X is —NH—, oxygen atom or sulfur atom;Y is —NR1—, oxygen atom, sulfur atom, sulfoxide or sulfone;Z is a single bond or —NR2—;R1 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group;R2 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group;l is an integer of from 0 to 15;m is an integer of 2 or 3; andn is an integer of from 0 to 3).The compound of the present invention is useful as a pharmaceutical composition, particuarly as an inhibitor of acyl coenzyme A cholesterol acyltransferase (ACAT).

This invention relates to a novel protein having a lecithin-cholesterol acyltransferase-like activity, etc. or its salt, a precursor protein of the protein or its salt, a partial peptide of the protein or its salt; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein, a pharmaceutical composition comprising the protein, the partial peptide or its salt; and an antibody to the protein or the partial peptide. The protein, the partial peptide or its salt, and the DNA are useful as an agent for treating or preventing arteriosclerosis, atherosclerosis, hyperlipidemia, hypercalorism, obesity or hypertriglyceridemia. The antibody can be used in assay of the protein, the partial peptide or its salt. The protein, the partial peptide or its salt is useful as a reagent for the screening for candidate medical compounds.

The present invention is directed to lecithin:cholesterol acyltransferase-like polypeptides (LCAT) and acyl CoA:cholesterol acyltransferases-like polypeptides (ACAT). The invention provides polynucleotides encoding such cholesterol:acyltansferases-like polypeptides, polypeptides encoded by such polynucleotides, and the use of such polynucleotides to alter sterol composition and oil production in plants and host cells. Also provided are oils produced by the plants and host cells containing the polynucleotides and food products, nutritional supplements, and pharmaceutical composition containing plants or oils of the present invention. The polynucleotides of the present invention include those derived from plant sources.

The invention provides compounds, pharmaceutical compositions and methods for treating atherosclerosis, coronary heart disease, thrombosis, and for decreasing or prevention of accumulation of cholesterol in a subject by modifying LCAT polypeptide.

Nucleic acid compositions encoding novel ACAT proteins, as well as the novel ACAT-2 proteins, (ACAT-2) are provided. Also provided are methods of producing the subject nucleic acid and protein compositions. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies for disease conditions associated with ACAT-2 activity.

The present invention relates to insecticidal compositions comprising compounds having an inhibitory activity versus acyl CoA:cholesterol acyltransferase (ACAT) or salts thereof as effective ingredients. The compounds having inhibitory activity versus ACAT have an excellent insecticidal effect by inhibiting sterol metabolism in noxious insects. Therefore, the compounds of the present invention can be used as safe and effective insecticides.

The invention provides a combined medication combination for tumor immunotherapy. The combined medication combination contains an effective dose of an acyl coenzyme A: cholesterol acyltransferase ACAT1 inhibitor and an effective dose of an immune detection point blocking antibody. The invention further provides a combined medication method for the tumor immunotherapy. By inhibiting the acyl coenzyme A: cholesterol acyltransferase ACAT1, the killing activity of CD8 T cells to tumors can be enhanced, and the acyl coenzyme A: cholesterol acyltransferase ACAT1 and the immune detection point blocking antibody can generate a synergic effect in combined medication, so that the inhibition to the tumors can be further enhanced.

The invention belongs to the technical field of biology, relates to a tumor immunotherapy drug target and application thereof, discloses application of acyl-coenzyme A: cholesterol acyltransferase ACAT1 serving as a drug target on one hand, and provides a method for in-vitro screening a tumor immunotherapy drug on the other hand, According to the method, a gene of acyl-coenzyme A: cholesterol acyltransferase ACAT1 or acyl-coenzyme A: cholesterol acyltransferase ACAT1 serving as a drug object is used for selecting the inhibitor of acyl-coenzyme A: cholesterol acyltransferase ACAT1 as a tumor immunotherapy candidate primary screening medicine. A new target is provided to the tumor immunotherapy drug, and a new platform is provided to screening of tumor immunotherapy drugs.

The invention relates to a pharmaceutical use of styrax. The invention particularly relates to use of the styrax in the preparation of acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, and the styrax can be prepared into injections, oral tablets, capsules and a variety of preparations for being applicable to preventing and treating atherosclerosis, hyperlipidemia and other diseases. Furthermore, the styrax can be used as a preventive drug or a therapeutic agent for angina, myocardial infarction, cerebral infarction, Alzheimer's disease, acute coronary syndrome, PTCA or posterior coronary artery re-stenosis with stent and other diseases. The styrax can also be used as the therapeutic agent for regulating the functions of sebaceous glands and inhibiting excessive production of sebum, thereby being used for treating oily skin, acne, seborrhea, acne-like injuries caused by corticosteroids and other diseases.

Nanostructures having an inorganic core and a lipid layer capable of binding a lecithin:cholesterol acyltransferase (LCAT) activator such as an apolipoprotein are provided herein. Methods of using the nanostructures and related devices and compositions for assessing the risk of developing a disease or condition or treating the disease or condition are also provided.

The invention discloses new application of a substance for inhibiting genetic expression and / or protein activity of acyl coenzyme A / cholesterol acyltransferase-1. According to the application, the inhibitor can be used for preparing drugs for preventing and / or treating cancer; the inhibitor can be used for preparing drugs for preventing and / treating cancer spreading and metastasis; the inhibitor can be used for preparing drugs for promoting apoptosis of cancer cells; the inhibitor can be used for preparing drugs for inhibiting cancer cells from being transformed into cancer; the inhibitor canbe used for preparing drugs for inhibiting in vitro proliferation growth of the cancer cells. Through experiments, the inventor proves that the acyl coenzyme A / cholesterol acyltransferase-1 (ACAT1 / SOAT1) is obviously highly expressed in liver cancer tissue, and the high enrichment value of the acyl coenzyme A / cholesterol acyltransferase-1 shows that prognosis of a liver cancer patient is poor. TheACAT1 / SOAT1 inhibitor can effectively inhibit growth of human liver cancer cells and other cancer cells in the cellular level, and the inhibitor can used as a candidate drug target of cancers, especially the liver cancer.

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin / kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

The invention relates to application of an acyl-coenzyme A: cholesterol acyltransferase-2 (ACAT2) inhibitor in liver cancer growth inhibition. Concretely, the inhibition of the activity of the ACAT2 can effectively inhibit the growth of human liver cancer cells and transplanted tumors respectively in cellular and animal levels, and the inhibitory effect is generated through accumulating intracellular cholesterol metabolites by blocking the secretion and excretion of ACAT2-mediated cholesterol metabolites. The accumulation of the cholesterol metabolites has effects on promoting the apoptosis of liver cancer cells and inhibiting the growth of liver cancer; the excretion of the cholesterol metabolites can remove the inhibitory effect.

The present invention is a method for identifying compounds that are allosteric and / or other novel ACAT inhibitors that is based on the novel finding that pregnenolone is a substrate for ACAT; esterification of pregnenolone by ACAT is dramatically activated when cholesterol is present in the assay. The method comprises measuring the esterification of pregnenolone by ACAT under two different conditions: with cholesterol, or without cholesterol. This method can be used to test and categorize various candidate ACAT inhibitors as allosteric or other novel ACAT inhibitors, or it can be used in high-throughput screening for identifying such ACAT inhibitors.

The present invention provides a method for the assessment of cholesterol esterification through physiologically relevant pathways and incorporates the function of individual subject's endogenous HDL particles. This ex vivo approach avoids the use of an artificial substrate and provides for determination of LCAT activity that includes both the contribution of a subject's endogenous HDL function and endogenous LCAT protein, and is therefore a significant improvement to the biologic relevance.

The invention discloses the application of egonol-type benzofuran and glycosides thereof in the preparation of an ACAT (Acyl-CoA:Cholesterol Acyltransferase) inhibitor, provides the application of egonol-type benzofuran as shown in general formula I and glycosides thereof in the preparation of the ACAT inhibitor, and further provides the drug combination of the ACAT inhibitor, which contains egonol-type benzofuran and glycosides thereof with the active component being shown in the general formula I. The egonol-type benzofuran and the glycosides thereof can be prepared into various forms of drug, such as tablets, capsules and the like, because of the significant effect of the ACAT inhibitor thereof. The invention is suitable for preventing and treating diseases, such as angina, myocardial infarction, cerebral infarction, Alzheimer's disease, acute coronary syndromes (ACS), percutaneous transluminal coronary angioplasty (PTCA) or post-stenting coronary restenosis; and the invention, as a therapeutic agent for regulating the sebaceous gland function and inhibiting the excessive production of sebum, is also suitable for curing diseases, such as oily skin, acne, seborrhea, acne-like lesion caused by corticosteroid and the like.

The present invention includes methods for treating Niemann-Pick Type C disease through administration of inhibitors of acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1). ACAT inhibitors are used to treat symptoms of Niemann-Pick Type C disease and prolong survival of patients with the disease, either alone or in combination with other treatments.

The invention relates to an application of a minimal heterodimer partner in blood lipid regulation. Through the modes of reporter genes and adenovirus over expression, the inventor finds that a minimal heterodimer partner (SHP) can down-regulate the expression of acyl-CoA cholesterol acyltransferase 2 (ACAT 2), and thus finds that the minimal heterodimer partner polynucleotide molecule or protein is applicable to the preparation of medicaments for treating hyperlipidemia diseases. Through the reduction of ACAT 2 by SHP adenovirus over expression, a new approach for blood lipid regulation is provided.

A use of a substance for inhibiting SOAT1 gene expression and / or protein activity. The use is selected from at least one of: (a) Preparation of kits for liver cancer diagnosis; (b) Preparation of kits for liver cancer prognosis; (c) Preparation of companion diagnostic kits for treatment of liver cancer; (d) For the preparation of drugs for the prevention and / or treatment of cancer; (e) For the preparation of drugs for the prevention and / treatment of cancer spread and metastasis; (f) For the preparation of drugs that promote the apoptosis of cancer cells; (g) For the preparation of drugs for inhibiting cancer cell formation; (h) For the preparation of drugs that inhibit the proliferation and growth of cancer cells in vitro. Experiments have shown that SOAT1 is highly expressed in liver cancer tissues and serum, and its high abundance indicates poor prognosis of liver cancer patients.

A therapeutic agent or prophylactic agent for a disease requiring an anti-foaming action for a cell and / or an inhibitory action for acyl-CoA cholesterol acyltransferase in treatment or prevention, characterized in that the therapeutic agent or prophylactic agent comprises as an effective ingredient a processed product derived from Peucedanum japonicum.

By this invention, novel nucleic acid sequences encoding for acyl-CoA: cholesterol acyltransferase (ACAT) related proteins are provided, wherein said ACAT-like protein is active in the formation of a sterol ester and / or triacylylgycerol from a fatty acyl-CoA and sterol and / or diacylglycerol substrates. Also considered are amino acid and nucleic acid sequences obtainable from ACAT-like nucleic acid sequences and the use of such sequences to provide transgenic host cells capable of producing sterol esters and / or triacylglycerols.

The invention relates to a synergistic composition of naturally occurring substances, which is particularly effective in the treatment of hypercholesterolemia. The composition of the invention comprises at least one substance having 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity, a substance having cytochrome CYP7A1 expression increasing activity, a substance having inhibitoryactivity against the enzyme Acyl-CoA: cholesterol acyltransferase ACAT1 and ACAT2 isoforms, procyanidins, and optionally, coenzyme Q10 and phytosterols.

A composition comprising an active agent that inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) is provided. With the composition, food intake can be suppressed, and / or body weight can be reduced, and / or metabolic disorders can be prevented and / or treated.

The invention discloses a novel compound (2S,3S,4R,9E)-2-[(2'R)-2'-hydroxyl-nonacosane amide]-octadecanoic-1,3,4-triol deriving from great burdock roots. The structural formula of the compound is shown in the description. The compound has a selection inhibition effect on cholesterol acyltransferase, can be effectively used for controlling and treating diseases including hyperlipidemia, atherosclerosis and coronary heart disease, and has broad research, development and application prospects. The number of steps for preparing the compound is small, operation is easy, and the obtained compound is natural and free of toxicity.