34 results about "3-hydroxy-3-methylglutaryl-coenzyme A" patented technology

Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are useful as antihypercholesterolemic agents and are represented by the following general structural formula (II):

Disclosed are the uses of specific genes of the mevalonate and isoprenoid biosynthetic pathways, and of inactive gene sites (the pseudogene) to (1) enhance biosynthesis of isopentenyl diphosphate, dimethylallyl diphosphate and isoprenoid pathway derived products in the plastids of transgenic plants and microalgae, (2) create novel antibiotic resistant transgenic plants and microalgae, and (3) create a novel selection system and / or targeting sites for mediating the insertion of genetic material into plant and microalgae plastids. The specific polynucleotides to be used, solely or in any combination thereof, are publicly available from GeneBank and contain open reading frames having sequences that upon expression will produce active proteins with the following enzyme activities: (a) acetoacetyl CoA thiolase (EC 2.3.1.9), (b) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase (EC 4.1.3.5), (c) HMG-CoA reductase (EC 1.1.1.34), (d) mevalonate kinase (EC 2.7.1.36), (e) phosphomevalonate kinase (EC 2.7.4.2), (f) mevalonate diphosphate decarboxylase (EC 4.1.1.33), (g) isopentenyl diphosphate (IPP) isomerase (EC 5.3.3.2), and (h) phytoene synthase (EC 2.5.1.32).

The present invention describes novel nitrosated and / or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and / or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and / or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and / or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and / or preventing renal toxicity; and for treating and / or preventing other disorders resulting from elevated levels of cyclooxygenase-2.

A method for treating age related macular degeneration (AMD) using an insulin preparation applied topically to the conjunctival sac of the affected eye. Another aspect of this invention is using antiangiogenic adjuvant therapeutic agents such as bevacizumab, ranibizumab, pegaptanib, etanercept, instilled in to the afflicted eye conjunctival sac with insulin to prevent further formation of new blood vessels, and shrink the existing pathologically formed blood vessels and reduce the edema in wet AMD. This method incorporates putting the patients on low fat diet, aerobic exercise, ketamine-a NMDA blocker, reducing the blood cholesterol using adjuvant therapeutic agents selected from Statins, that are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A, (i.e. HMG-Co A) reductase which in turn reduce drusen formation that leads to AMD, combined with insulin ophthalmic drops.

The present disclosure describes methods for treating or preventing Type 1 diabetes mellitus in juveniles, particularly in juveniles newly diagnosed with Type 1 diabetes. This prevention or treatment of Type 1 diabetes is achieved by administering one or more therapeutic agents to a juvenile in need, wherein the therapeutic agent is, for example, a competitive inhibitor of mevalonate synthesis, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, or an inducer of AMP protein kinase (AMPK) activity. In certain embodiments, juveniles with Type 1 diabetes are treated with an HMG-CoA reductase inhibitor such as a statin, thereby decreasing the destruction of islet cells, or maintaining endogenous insulin production, in the juvenile.

The present invention relates to substituted pyrrole derivatives, which can be used as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Compounds disclosed herein can function as cholesterol lowering agents and can be used for the treatment of cholesterol-related diseases and related symptoms. Processes for the preparation of disclosed compounds are provided, as well as pharmaceutical compositions containing the disclosed compounds, and methods of treating cholesterol-related diseases and related symptoms.

The invention describes novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and / or, optionally, at least one therapeutic agent, such as, steroids, nonsterodal anti-inflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2 antagonists, antineoplastic agents, antiplatelet agents, thrombin inhibitors, thromboxane inhibitors, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton-pump-inhibitors, isoprostane inhibitors, and mixtures thereof. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and / or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and / or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and / or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and / or preventing renal toxicity or other toxicities; for treating and / or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

Disclosed herein are novel compounds of formula (I), and uses thereof. The compounds of Formula (I) are inhibitors of histone deacetylases (HDACs) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR). Also provided are methods of using the compounds of Formula (I) for inhibiting the activity of HDACs and HMGR, treating diseases associated with HDACs or HMGR (e.g., cancer, hypercholesterolemia, an acute or chronic inflammatory disease, autoimmune disease, allergic disease, pathogen infection, neurodegenerative disease, or a disease associated with oxidative stress,

The invention belongs to the technical field of biology, and particularly relates to a dipeptide capable of being combined with angiotensin converting enzyme to inhibit activity of the angiotensin converting enzyme and inhibit activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The invention particularly discloses a dipeptide ST with double functions of lowering blood pressure and lowering blood fat, wherein the amino acid sequence of the dipeptide ST is Ser-Thr. The invention also discloses application of the dipeptide ST in preparing ACE (angiotensin converting enzyme) inhibitory peptide and / or HMG-CoA reductase inhibitory peptide.

The invention relates to the technical field of biological medicine, in particular to a bisindole compound as well as a preparation method and an application thereof. The preparation method comprises the following steps: an FG216 strain is inoculated to a seed medium and cultured on a shaking table for 1-3 days under the conditions of 22-28 DEG C and 160-220 r*min<-1>; then a seed culture solution is inoculated to a fermentation medium and cultured on the shaking table for 5-10 days under the conditions of 22-28 DEG C and 160-220 r*min<-1>; mycelia of a fermentation solution are separated and extracted with methanol or ethyl acetate, a methanol extracting solution or an ethyl acetate extracting solution is taken as a fermentation product of the FG216 strain, and an elution peak reserved for 15.6 min in HPLC (high performance liquid chromatography) is the bisindole compound. The preparation method has the advantages of high yield and low cost. The prepared bisindole compound can inhibit HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase effectively, has low IC50 (half maximal inhibitory concentration) and can be used for preparing drugs for treating arteriosclerosis diseases.

A pharmaceutical composition for inhibiting inflammation, comprising (a) hyaluronic acid, (b) a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, and (c) a pharmaceutically acceptable carrier, is provided. Also provided is a method for inhibiting inflammation in a mammal, comprising administrating to the mammal an effective amount of a composition comprising (a) hyaluronic acid and (b) an HMG-CoA reductase inhibitor.

A novel solid oral dosage form comprising a therapeutically effective amount of hydrophobic pharmacological active ingredient and at least one particle separating agent preferably selected from a class of wetting agents, prepared without or with minimum amount of a disintegrating agent. The hydrophobic pharmacological active ingredient active ingredient belongs to the class of angiotensin receptor blocking agents preferably is valsartan optionally in combination with hydrochlorothiazide. The active ingredient may also be a class of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors preferably atorvastatin. The ratio of hydrophobic active ingredient to particle separating agent is about 20:1 to about 1:20. The process for the preparation of the novel solid oral dosage form comprises treating a hydrophobic active ingredient with at least one particle separating agent, and incorporating the treated hydrophobic active ingredient into a solid dosage form.

The invention discloses a camptotheca 3-hydroxy-3-methylglutaryl coenzyme A synthase gene, protein which is encoded by the camptotheca 3-hydroxy-3-methylglutaryl coenzyme A synthase gene and the use thereof. The 3-hydroxy-3-methylglutaryl coenzyme A synthase gene which is provided by the invention has a nucleotide sequence or a homologous sequence which adds, replaces, inserts or losses one or a plurality of nucleotides or allele thereof and the nucleotide sequence which is derived from the 3-hydroxy-3-methylglutaryl coenzyme A synthase gene, which are displayed in the SED ID No.1. The protein which is encoded by the gene has an amino acid sequence or the homologous sequence which adds, replaces, inserts or losses one or a plurality of amino acids, which is displayed in the SEQ ID No.2. The 3-hydroxy-3-methylglutaryl coenzyme A synthase gene which is provided by the invention can increase the content of camptothecin alkaloid in plants such as camptotheca and the like through the genetic engineering technology and can be used in research and industrialization for increasing the content of the camptothecin alkaloid through utilizing the transgenic technology.

Disclosed herein are compositions and methods for decreasing vascular permeability in a blood vessel and treating or preventing conditions associated with defects or injuries of vascular endothelium. For example, the disclosed compositions and methods can be used to treat a vascular dysplasia such as cerebral cavernous malformation (CCM). These methods relate generally to the use of compositions that inhibit RhoA GTPase levels or activity, such as inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.

The invention relates to the technical field of biomedicines, in particular to a compound medicine for reducing blood pressure and blood fat and a preparation method thereof. The compound medicine for reducing blood pressure and blood fat consists of a thiazine hypotensor and a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and can simultaneously treat hypertension and hyperlipidemia; the hypotensor and a hypolipidemic are not required to be taken simultaneously; the compound medicine is used for reducing blood pressure and blood fat by synergistic effect of the thiazine hypotensor and the HMG-CoA reductase inhibitor, improves compliance of patients and reduces adverse reaction; the compound medicine has a good therapeutic effect on hypertension and hyperlipidemia in clinical trials; and moreover, the invention also provides the preparation method thereof, technical bottleneck problems are solved, the thiazine hypotensor and the HMG-CoA reductase inhibitor can be stably used in the compound medicine, respective properties of the thiazine hypotensor and the HMG-CoA reductase inhibitor are not affected, and patients suffering from hypertension and hyperlipidemia are simultaneously effectively treated.

The invention relates to a medicament containing theophylines and statins. In the invention, the theophylines and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor form a compound to obtain excellent synergistic effect. The medicament compound greatly reduces the toxic and side effect of aminophylline when used alone, and the pharmacy security is improved.

The invention belongs to the technical field of biology, and particularly relates to a dipeptide capable of being combined with angiotensin converting enzyme to inhibit activity of the angiotensin converting enzyme and inhibit activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The invention particularly discloses a dipeptide QD with double functions of lowering blood pressure and lowering blood fat, wherein the amino acid sequence of the dipeptide QD is Gln-Asp. The invention also discloses application of the dipeptide QD in preparing ACE (angiotensin converting enzyme) inhibitory peptide and / or HMG-CoA reductase inhibitory peptide.

Chemical syntheses and medical uses of novel modulators of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and diastereomeric mixtures of isomers, individual diastereomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, the chemical synthesis thereof, and the medical use of such compounds for the treatment and / or management of hypercholesterolemia, dyslipidemia, coronary artery disease, atherosclerosis, metabolic syndrome, a hyperproliferative disease such as colorectal cancer, prostate cancer, and melanoma, a neurodegenerative disease such as cerebral ischemia, Alzheimer's disease, and Parkinson's disease are described.

The invention discloses application of atorvastatin in preparation of medicines for treating uterine fibroid. The medicine is used for inhibiting the growth of immortalized uterine fibroid cells and primary uterine fibroid cells, including inhibiting of cell proliferation, and promoting of cell apoptosis. The atorvastatin is used for inhibiting the growth of uterine fibroid cells by down-regulating the expression of proliferation protein PCNA and anti-apoptosis protein Bc1-2, up-regulating the expression of apoptosis protein cleaved-caspase 3 and Bim, inhibiting a signal channel of MAPK (mitogen-activated protein kinase), down-regulating the activity of p-ERK1 / 2 (phospho-extracellular regulated protein kinases 1 / 2), inhibiting the activity of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A), and inhibiting the mevalonate pathway. The application of the blood fat-decreasing medicine, namely the atorvastatin, in the treatment of the uterine fibroid is proofed by the experiment, and the effect of inhibiting the growth of the uterine fibroid is obtained.

The present invention relates to substituted pyrrole derivatives of Formula (I), wherein (Y), with the proviso that one of R2, R4 and R5 is a heterocycle and with the further provision that if R2 is not a heterocycle then either R4 or R5 alone is not unsubstituted pyridyl, which can be used as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Compounds disclosed herein can function as cholesterol lowering agents and can be used for the treatment of cholesterol-related diseases and related symptoms. Processes for the preparation of disclosed compounds are provided, as well as pharmaceutical compositions containing the disclosed compounds, and methods of treating cholesterol-related diseases and related symptoms.

The present invention provides novel compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) are inhibitors of histone deacetylases (HDACs) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR). Also provided are methods of using the compounds and pharmaceutical compositions for inhibiting the activity of HDACs and HMGR, treating diseases associated with HDACs or HMGR (e.g., cancer, hypercholesterolemia, an acute or chronic inflammatory disease, autoimmune disease, allergic disease, pathogen infection, neurodegenerative disease, and a disease associated with oxidative stress), or inhibiting drug resistance of cancer cells.

The present disclosure describes methods for treating Type 1 diabetes mellitus in juveniles. This treatment of Type 1 diabetes is achieved by administering one or more therapeutic agents to a juvenile in need, wherein the therapeutic agent is, for example, a competitive inhibitor of mevalonate synthesis, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, or an inducer of AMP protein kinase (AMPK) activity. In certain embodiments, juveniles with Type 1 diabetes are treated with an HMG-CoA reductase inhibitor such as a statin.

The invention relates to a medicament containing theophylines and statins. In the invention, the theophylines and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor form a compound to obtain excellent synergistic effect. The medicament compound greatly reduces the toxic and side effect of aminophylline when used alone, and the pharmacy security is improved.

The invention belongs to the technical field of biology, and particularly relates to a dipeptide capable of being combined with angiotensin converting enzyme to inhibit activity of the angiotensin converting enzyme and inhibit activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The invention particularly discloses a dipeptide DL with double functions of lowering blood pressure and lowering blood fat, wherein the amino acid sequence of the dipeptide DL is Asp Leu. The invention also discloses application of the dipeptide DL in preparing ACE (angiotensin converting enzyme) inhibitory peptide and / or HMG-CoA reductase inhibitory peptide.

The invention belongs to the field of genetic engineering, and particularly relates to application of an HMGCR(3-hydroxy-3-methylglutaryl-CoA reductase, 3-hydroxy-3-methylglutaryl coenzyme A reductase1) gene in improvement of titer and infectivity of lentivirus. The invention discloses an HMGCR gene and further discloses a eukaryotic expression vector comprising the HMGCR gene. The nucleotide sequence of the HMGCR gene is shown as SEQ ID NO:1. A pcDNA4-HMGCR vector and the plasmid of a lentivirus packaging system jointly transfect cells, so that the titer and infectivity of the lentivirus canbe greatly improved while the capability of the lentivirus produced by cells is obviously improved, and a novel large-scale high-infectivity lentivirus packaging method is provided for basic researchand clinical application fields. In addition, application has the advantages of simple operation steps, low cost, non-animal source production and the like.