2015 results about "Mechanism of action" patented technology

The invention provides substituted diaryl compounds as shown in general formula (I) or their pharmaceutically acceptable salts, and also provides a preparation method; a class of novel broad-spectrum antiviral compounds and pharmaceutical salts targeting cytokines are screened and obtained through studies on structure-activity relationship and action mechanism of active compounds; the compounds not only have significant broad-spectrum antiviral activity, but also have the advantages of low toxicity and good pharmaceutical properties.

Patients inflicted with various clustering chronic diseases require treatment with multiple drugs having distinct mechanisms of action. Accordingly, patients with multiple conditions suffer from cumulative side effects of multiple drugs as well as drug-drug interactions. Embodiments, agents, compounds or drugs of the present invention, such as sesquiterpenes, e.g., Zerumbone, replace an equal or larger number of approved drugs during patient treatment. Examples of disorders prevented or ameliorated by administration of the formulations of this invention include but are not limited to inflammatory diseases that may be, oncological, genetic, ischemic, infectious, neurological, hematological, ophthalmological, rheumatoid, orthopedic, neurological, hematological, kidney, vascular, dermatological, gynecological, or obstetric. The present invention further relates to a method of identifying agents, compounds or drugs useful in preventing or treating CDCP related diseases and conditions as well as other disorders, diseases and conditions treatable or preventable by the same agents, compounds or drugs.

The present invention is, generally, directed to the use of betulinic acid and derivatives thereof for the treatment of neuroectodermal tumors. The present invention is based on the discovery that betulinic acid and its derivatives are potent anti-neuroectodermal agents. As disclosed herein, betulinic acid and its derivatives are useful for the treatment of neuroectodermal tumors, including, due to its distinct mechanism of action, neuroectodermal tumors that are resistant to conventional chemotherapeutical agents. In addition to the new use of known compounds, the invention discloses novel compounds and pharmaceutical compositions for the treatment of neuroectodermal tumors.

The present invention relates to the field of medical treatments for diseases and disorders. More specifically, the present invention relates to the use of the lanthionine synthetase component C-like (LANCL) proteins as therapeutic targets for novel classes of anti-inflammatory, immune regulatory and antidiabetic drugs. This includes but it is not limited to abscisic acid (ABA), ABA analogs, benzimidazophenyls, repurposed drugs or drug combinations, including thiazolidinediones (TZDs); naturally occurring compounds such as conjugated diene fatty acids, conjugated triene fatty acids, isoprenoids, and natural and synthetic agonists of peroxisome proliferator-activated receptors that activate this receptor through an alternative mechanism of action involving LANCL2 or other membrane proteins to treat or prevent the common inflammatory pathogenesis underlying type 2 diabetes, atherosclerosis, cancer, some inflammatory infectious diseases such as influenza and autoimmune diseases including but not limited to inflammatory bowel disease (Crohn's disease and Ulcerative colitis), rheumatoid arthritis, multiple sclerosis and type 1 diabetes and other chronic inflammatory conditions.

The invention discloses a complex probiotics for environmental remediation, a preparation method and application thereof. The complex probiotics is prepared from the following strains in weight proportion: 1 to 5 portions of photosynthetic bacteria, 1 to 3 portions of lactic acid bacteria, 0.5 to 1.5 portions of bacillus, 1.0 to 1.4 portions of actinomycete, 0.6 to 1.0 portion of microzyme, and 1 to 5 portions of filamentous fungus, wherein the contents of active bacteria in the strains are all between1,800 and 2,600 million per milliliter. The mechanism of action of the complex probiotics comprises that: the probiotics is used as a leading raw material and combined with other useful microbes to generate an oxidation resisting material, and the oxidation resisting material decomposes and oxidizes organic matters by oxidization, reduction, fermentation and the like, so that the harmful and poisonous materials are turned into unharmful and nontoxic materials, and the idea of changing wastes into valuables is realized. The complex probiotics is widely applied in environmental protection field of deodorizing in a washroom, reutilizing domestic garbage, treating odorous lakes and stagnant water, purifying tap water and a swimming pool and the like, and has low cost.

The invention provides a method of determining whether tumor cells or tissue is responsive to treatment with an ErbB pathway-specific drug. In accordance with the invention, measurements are made on such cells or tissues to determine values for total ErbB receptors of one or more types, ErbB receptor dimers of one or more types and their phosphorylation states, and/or one or more ErbB signaling pathway effector proteins and their phosphorylation states. These quantities, or a response index based on them, are positively or negatively correlated with cell or tissue responsiveness to treatment with an ErbB pathway-specific drug. In one aspect, such correlations are determined from a model of the mechanism of action of a ErbB pathway-specific drug on an ErbB pathway. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in ErbB pathway activation. After binding, molecular tags are released and separated from the assay mixture for analysis.

The invention searches the novel micromolecule inhibitor pyrazolo (1, 5-a) miazines compounds of cyclin-dependent kinase CDK9 (cyclin-dependent kinase) through the virtual screening of a computer, biometrically measures activity thereof, and validates interaction mechanism. The invention specifically comprises the following steps: the three-dimensional crystal conformation of the cyclin-dependent kinase family member CDK9 is obtained in a way of homology modeling; and micromolecule three-dimensional database is screened with DOCK (molecular docking). The invention uses a MTT tumor cell growth inhibition test to biometrically measures the activity of the selected compounds, researches the selected compounds pyrazolo (1, 5-a) miazines with high activety in a way of molecular mechanism, validates the inhibiting effect of the compounds to the activity of CDK9 kinase, and clarifies the interaction mechanism of the compounds for inhibiting the external activity and the molecule of various malignancies such as lung cancer, osteosarcoma, oophoroma, cervical carcinoma, breast cancer, etc.

Method for preparing 8-(3-aminopiperidin-1-yl)-xanthine derivatives (I) and their enantiomers and salts. Method for preparing 8-(3-aminopiperidin-1-yl)-xanthine derivatives of formula (I) and their enantiomers and salts by: (a) reacting an 8-X-xanthine (III) with 3-phthalimidopiperidine (A), or its enantiomer; (b) deprotecting the product (II); and (c) optionally conversion to salt. X : halo or sulfonate ester, especially bromo; R 1>phenylcarbonylmethyl, benzyl, naphthylmethyl, pyridinylmethyl, pyrimidinylmethyl, (iso)quinolinylmethyl, quinazolinylmethyl, quinoxalinylmethyl, naphthyridinylmethyl or phenanthridinylmethyl, all optionally substituted by one or two, same or different, Ra; R 2>1-3C alkyl, cyclopropyl or phenyl; R 3>2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, or 2-(fluoro, chloro, bromo, iodo, methyl, trifluoromethyl or cyano)-benzyl; Ra : hydrogen, fluoro, chloro, bromo, cyano, methyl, trifluoromethyl, ethyl, phenyl, methoxy, di- or tri-fluoromethoxy, or two Ra on adjacent C atoms complete OCH 2O or OCH 2CH 2O Independent claims are also included for the following: (1) (R) and (S)-3-phthalimidopiperidine as new compounds; and (2) methods for preparing the compounds of (1). [Image] [Image] - ACTIVITY : Antidiabetic; Antiarthritic; Anorectic; Osteopathic. No details of tests for these activities are given. - MECHANISM OF ACTION : Inhibition of dipeptidylpeptidase IV.

The invention discloses a simulation test device and a simulation test method for in-situ chemical and biological remediation of underground water. The simulation test device comprises a seepage slot, an inlet water buffer slot, an outlet water buffer slot, a water supply device and a liquid recovering bottle; the seepage slot is respectively communicated with the inlet water buffer slot and the outlet water buffer slot through porous water distribution baffles; the outer side of the outlet water buffer slot is provided with a drain hole with a valve; the seepage slot is provided with a row of injection wells at the upstream and a plurality of monitoring wells inside, and the monitoring wells are internally provided with water quality analysis probes; the tops of the seepage slot and the inlet water buffer slot are provided with a top sealed plate in which air inlets and air outlets are arranged; and the side wall of the seepage slot is provided with a pressure measuring pipe. The method comprises: filling with a medium, saturating with water, introducing polluted underground water by pumping, and adding a reagent for simulating the in-situ chemical and biological remediation process. The simulation test device is flexible, simple and convenient in design, low in test cost and strong in process controllability, can be used for researching the dynamic effect and the action mechanism for chemical and biological enhanced treating on organically-polluted underground water under an in-situ condition, and also can be used for observing the attenuation process of specific pollutants in underground water.

The invention discloses a targeted-FTO-gene-knockout sgRNA (small guide ribonucleic acid) and CRISP (clustered regularly interspaced short palindromic repeats)/Cas9 slow virus system and application thereof. The sgRNA is selected from FTOsgRNAsp2 or FTOsgRNAsp3 with the following DNA sequence. The sgRNA has high cutting efficiency for the FTO gene. When the sgRNA-containing CRISPR/Cas9 slow virus system is used for transfecting SV-HUC-1, the FTO protein expression level of the obtained cell strain is obviously lowered. Therefore, the sgRNA disclosed by the invention can effectively implement targeted FTO gene knockout; and after the sgRNA is established into the CRISPR/Cas9 slow virus system, the system can knock out the FTO gene to obtain the FTO-gene-knockout cell strain, thereby being beneficial to researching the action mechanism of FTO in the cell strain.

The invention relates to the field of recombinant antibodies for use in human cancer therapy. More specifically the invention provides compositions or mixtures of antibodies capable of binding human EGFR. Antibody compositions with 3 or more antibodies shown synergy in reduction of proliferation of representative cancer cell lines. Advantageous results have also been obtained with a composition comprising two different chimeric anti-hEGFR antibodies which show a new mechanism of action based on rapid and efficient receptor internalisation, induction of terminal differentiation and subsequent tumour eradication in an animal model. The antibodies of the invention can be manufactured in one bioreactor as a polyclonal antibody.

A drug delivery system is disclosed. The drug delivery system includes a recognitive polymeric hydrogel through which a drug is delivered by contacting biological tissue. The recognitive polymeric hydrogel is formed using a bio-template, which is a drug or is structurally similar to the drug, functionalized monomers, preferably having coamplexing sites, and cross-linking monomers, which are copolymerized using a suitable initiator. The complexing sites of the recognitive polymeric hydrogel that is formed preferably mimics receptor sites of a target biological tissue, biological recognition, or biological mechanism of action. The system in accordance with an embodiment of the intention is a contact lens for delivering a drug through contact with an eye.

This invention provides principles, methods and compositions for ascertaining the mechanism of action of pharmacologically important compounds in the context of network biology, across the entire scope of the complex pathways of living cells. Importantly, the principles, methods and compositions provided allow a rapid assessment of the on-pathway and off-pathway effects of lead compounds and drug candidates in living cells, and comparisons of lead compounds with well-characterized drugs and toxicants to identify patterns associated with efficacy and toxicity. The invention will be useful in improving the drug discovery process, in particular by identifying drug leads with desired safety and efficacy and in effecting early attrition of compounds with potential adverse effects in man.

The invention discloses a CRISPR-Cas9 targeted and knockout human breast cancer cell SLC30A1 gene and the specific sgRNA of the gene. Firstly, sgRNA for specific targeting of the SLC30A1 gene is obtained, and a base sequence of the sgRNA is shown in SEQ ID NO.1; secondly, the sgRNA of the SLC30A1 gene is constructed to a lentivirus vector system containing Cas9 proteins; finally, CRISPR/Cas9 lentivirus containing the sgRNA is infected with a human breast cancer cell MDA-MB-231 to obtain a cell strain of which the SLC30A1 protein expression level is obviously reduced. The CRISPR-Cas9 targeted and knockout human breast cancer cell SLC30A1 gene and the specific sgRNA of the gene disclosed by the invention have the advantages of simple operation steps, good sgRNA targetability and high cuttingefficiency on the SLC30A1 gene; in addition, the constructed CRISPR/Cas9 lentivirus system has the advantage of high knockout efficiency and can specifically knock out the SLC30A1 gene so as to obtain the human breast cancer cell having the SLC30A1 gene knocked out; therefore, a powerful tool is provided for further researching an action mechanism of the SLC30A1 in breast cancer cells.

The invention discloses a CRISPR/Cas9 targeted knockout human colorectal carcinoma cell DEAF1 gene and specific sgRNA thereof. The CRISPR/Cas9 targeted knockout human colorectal carcinoma cell DEAF1 gene and the specific sgRNA thereof are characterized in that: firstly, sgRNA of a second exon of the specific targeted DEAF1 gene is obtained and the base sequence of the sgRNA is shown as SEQ ID NO.1; secondly, the sgRNA of the DEAF1 gene is constructed into a lentiviral vector system, which contains Cas9 protein; finally, the CRISPR/Cas9 lentivirus containing the sgRNA is infected with human colorectal carcinoma cell HT-29 cell, so that a cell strain of which DEAF1 protein expression level is obviously reduced is obtained. The CRISPR/Cas9 targeted knockout human colorectal carcinoma cell DEAF1 gene disclosed by the invention has the advantages of simple operation steps, good sgRNA target ability and high cutting efficiency for the DEAF1 gene; in addition, the constructed CRISPR/Cas9 lentiviral vector system has the advantage of high knockout efficiency and can specifically knock out the DEAF1 gene to obtain the human colorectal carcinoma cells knocking out the DEAF1 gene, and therebya powerful tool is provided for further studying an action mechanism of DEAF1 in the colorectal carcinoma cells.

The present invention discloses CRISPR/Cas9 targeted knockout human intestinal cancer cell RITA gene and specific sgRNA thereof. First, sgRNA specifically targeted to a second exon of the RITA gene isobtained, and the base sequence of the sgRNA is as shown in SEQ ID NO. 1; secondly, a sgRNA lentiviral vector system of the RITA gene is constructed, and the sgRNA lentiviral vector system contains Cas9 protein; and finally human intestinal cancer HT-29 cells are infected with CRISPR/Cas9 lentivirus containing the sgRNA to obtain a cell line which is significantly reduced in RITA protein expression level. The invention has the advantages of simple operation steps, good sgRNA targeting property, and high RITA gene cutting efficiency; furthermore, the constructed CRISPR/Cas9 lentivirus system has the advantage of high knock-out efficiency and can specifically knock out the RITA gene to obtain RITA gene-knockout human intestinal cancer cells, and a powerful tool for the further study of theaction mechanism of RITA in the intestinal cancer cells is provided.

The invention provides a pesticide composition and application thereof, wherein the composition comprises the active components, namely JS399-19 and a triazole bactericide, and the composition is suitable for controlling agricultural diseases. The pesticide composition has the following advantages: (1) the composition shows excellent synergistic action in certain proportioning range, the sterilizing effect of the composition is improved obviously compared with a single agent, and simultaneously the dosage, the application labor and the cost of the pesticide are reduced, and harmful effect and pesticide residue to the environment are also reduced; (2) the two active components in the composition have different mechanisms of action, and the application of the composition can retard or overcome the drug resistance of pathogenic bacteria and prolong the service life of the single agent; and (3) the composition has wide control spectrum and can control various crop diseases.

The invention discloses a CRISPR-Cas9 targeted-knockout human colorectal cancer cell PPP1R1C gene and a specific sgRNA sequence. The invention comprises the following steps: firstly, acquiring sgRNA of a specific targeting PPP1R1C gene functional area, wherein a base sequence of the sgRNA is shown as SEQ ID NO.1; then, constructing an sgRNA-lentiviral vector system of the PPP1RQC gene, wherein thesystem contains Cas9 protein; and finally, infecting human colorectal cancer HT-29 cells with CRISPR/Cas9 lentivirus containing the sgRNA, so that a cell line that a PPP1R1C protein expression levelis obviously reduced is obtained. The invention is simple in operating steps, good in sgRNA targeting performance and high in cutting efficiency on the PPP1R1C gene; the constructed CRISPR/Cas9 lentiviral system is high in knockout efficiency and is capable of achieving specific knockout of the PPP1R1C gene, so that the human colorectal cancer cells that the PPP1R1C gene is knocked out is obtained; therefore, a powerful tool is provided for further researching an action mechanism of the PPP1R1C in the colorectal cancer cells.

A device is described for indicating the locking state of a fifth wheel coupling and an arrangement of a first and a second sensor. According to the prior art, the first sensor is arranged on the underside of the locking latch and monitors the position of the kingpin in relation to the locking latch. A second sensor that is used is an inductive proximity switch that monitors a safety mechanism against loosening. In practice, this type of positioning of the first sensor has led to damage of the locking latch and the first sensor, while the signals of the second sensor were often false signals. Thus, the object of the invention is to provide a device for indicating the locking state, which maximizes operational availability and minimizes false signals. A further object of the invention is to optimize the arrangement of the first and the second sensor. These objects are attained by arranging the first sensor detecting the kingpin in the area of the locating hole and configuring the second sensor as a magnetically sensitive sensor that interacts with a magnet mounted on the operating lever. The two sensors are based on different mechanisms of action.

The invention belongs to the technical field of cement auxiliary-grinding agents, and in particular to a preparation method for a cement auxiliary-grinding strengthener of a polyethylene glycol amine ester carboxylic acid system. The preparation method comprises the following steps: (1) performing esterification reaction on alcohol amines and unsaturated carboxylate in a molar mass ratio to obtain esterification monomers which contain polar groups, such as hydroxyl and carboxyl; (2) adding unsaturated large monomers and water into a reaction container, stirring, heating and dissolving, respectively adding an initiator, the esterification monomers and a chain transfer agent dropwise, preserving the heat after the reaction is performed for a certain period of time, and adjusting the pH of a solution to be neutral after the reaction is completed so as to prepare the cement auxiliary-grinding strengthener of the polyethylene glycol amine ester carboxylic acid system. The cement auxiliary-grinding strengthener fully plays the action mechanism of the polar functional groups, such as the hydroxyl and the carboxyl, on cement; when the using amount is 0.01 to 0.1 percent of the mass of the cement, the yield each grinding machine per hour is improved by 12 to 25 percent, the 3-day strength of the cement can be increased by 2 to 5 MPa, the 28-day strength of the cement can be increased by 4 to 8 MPa, and the aims of stable performance and remarkable effects of auxiliary grinding and strengthening are fulfilled.

A drug delivery system is disclosed. The drug delivery system includes a recognitive polymeric hydrogel through which a drug is delivered by contacting biological tissue. The recognitive polymeric hydrogel is formed using a bio-template, which is a drug or is structurally similar to the drug, functionalized monomers, preferably having complexing sites, and cross-linking monomers, which are copolymerized using a suitable initiator. The complexing sites of the recognitive polymeric hydrogel that is formed mimic receptor sites of a target biological tissue, biological recognition, or biological mechanism of action. A system in accordance with some embodiments is a contact lens for delivering a drug through contact with an eye. In some embodiments, the drug is an anti-microbial, such as an anti-fungal agent for treatment of large animals. In some embodiments, a comfort molecule hyaluronic acid (HA) is delivered. In some embodiments, ketotifen fumarate (anti-histamine) and/or diclofenac sodium (anti-inflammatory) are delivered.