24 results about "Cellular activity" patented technology

Provided herein are compositions comprising a particle comprising a library encoded bead (e.g., DEL bead) coated in a polymeric matrix forming a core-shell particle, wherein the core-shell particle is further inside a 3D tissue culture. Also provided herein are methods of making such particles, and methods of using such particles for drug discovery such as identification of bioactive compounds via high-throughput cellular activity-based phenotypic screens of DNA-encoded chemical library beads.

The present application relates to a quinazoline derivative of general formula (I) or stereoisomer, pharmaceutically acceptable salt, solvate, or tautomer, which can selectively inhibit CDK9 and / or TNIK, and has good enzymatic and cellular activity.

The present invention relates to 1,2-dicarboxamide compounds of Formula (I); pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, N-oxides or combination thereof, wherein 'X', 'Y', 'Z', ring A, ring B, R1, R2, R3, R4, R5, R6, 'm' and 'n' are as defined herein. The present invention also relates to 1,2-dicarboxamide compounds that modulate cellular activities like proliferation, differentiation, adhesion, migration and apoptosis by modulating protein kinase enzymatic activity. In particular the invention relates to compounds which inhibit, regulate, and / or modulate tyrosine kinases such as FLT1 (VEGFR1), FLT4 (VEGFR3), KDR (VEGFR2), MET (C-Met), MERTK (c-Mer), RET, AXL, TEK (TIE 2) and EGFR. The present disclosure relates to 1,2-dicarboxamide compounds for use in modulating kinase enzymatic activity and accordingly modulating kinase-dependent associated diseases and conditions such as cancers like Thyroid carcinoma, Ovarian carcinoma, Pancreatic carcinoma, Prostatic carcinoma, Renal cell carcinoma, Hepatocellular carcinoma, Breast carcinoma, Colorectal carcinoma, Oral squamous cell carcinoma, Colorectal, Lung adenocarcinoma or Endometrial cancer.

The present disclosure generally relates to, inter alia, a new class of chimeric Notch receptors containing a fully humanized transcriptional effector, engineered to modulate gene expression and cellular activities in a ligand-dependent manner. The new chimeric Notch receptors surprisingly retain the ability to transduce signals in response to ligand binding despite that the Notch extracellular subunit (NEC), which includes the negative regulatory region (NRR) previously believed to be essential for the functioning of Notch receptors is completely absent. In addition, the new receptors described herein incorporate an extracellular oligomerization domain to promote oligomer formation of the chimeric receptors. Also provided are compositions and methods useful for producing such receptors, nucleic acids encoding same, engineered cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and / or for the treatment of various diseases such as cancers.

Synthetic polymer networks have been introduced into mammalian cells, rendering them incapable of dividing while retaining cellular activity. A variety of mammalian cell types, useful for example in tissue regeneration and reducing inflammation in mammals, have been generated by the inventors and found to produce a number of desirable growth factors, chemokines, cytokines and other factors, indicating uses in therapy for mammals in need of these factors.

This invention provides an N-aryl-N-arylpropynyl-arylacetamide compound and its pharmaceutical uses. The provided compounds include their prodrugs, tautomers, stereoisomers, solvates, isotopic derivatives, or pharmaceutically acceptable salts thereof. The compounds of this invention can serve as the first covalent inhibitor of POLQ. In vitro enzyme activity inhibition studies show that the compounds of this invention have strong inhibitory effects on POLQ enzymes and can serve as promising compounds for the treatment of POLQ-mediated diseases. Further studies have shown that typical compounds I-1, I-13, and I-25 have considerably long-lasting inhibitory activity against POLQ enzymes and good cellular activity. The synthetic method of this invention is simple and convenient, facilitating large-scale industrial production and application. The general structural formula of this invention is shown in Formula I:

The invention provides for compositions comprising phosphorous containing tricyclic compounds, including phthalazin-1(2H)-one derivatives. The compounds are potent inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), particularly PARP-1 and potentially PARP-2. The also show good cellular activity in inhibiting poly(ADP-ribose) oligomer formation. The compounds may be useful as mono-therapy or in combination with other therapeutic agents in the treatment conditions where PARP is implicated, such as cancer, inflammatory diseases and ischemic conditions. Thus, also provided are methods for the treatment of a condition where PARP is implicated comprising administering to an effective amount of a compound of the invention to an individual in need thereof.

To provide a method for treating cancer and autoimmune diseases by in vivo transforming immunosuppressive tumor-associated macrophages (TAMs) that support cancer growth and metastasis into highly activated tumoricidal macrophages.SOLUTION: Provided is a method for altering the activation state of macrophages within a tumor in vivo, comprising administering to a tumor site nanoparticles comprising a poly(β)-amino ester core and a polyglutamic acid coating, in which in vitro transcribed mRNA encoding (i) one or more interferon regulatory factors (IRFs) and (ii) IKKβ are encapsulated within the core, the activation state of the macrophages being altered from an inactivated state to an activated state.SELECTED DRAWING: None

The invention relates to an antibody drug conjugate containing a phenanthroquinolizidine compound as shown in a formula I, a pharmaceutical composition, a preparation method of the antibody drug conjugate, and application of the antibody drug conjugate in prevention and / or treatment of cell activity abnormity related diseases, including but not limited to prevention and / or treatment of tumor diseases. The antibody drug conjugate can realize tumor enrichment, eliminate or reduce toxic and side effects caused by the phenanthroquinolizidine compound acting on non-disease tissues, and improve the treatment effect.

An apparatus for measuring brain cell activity in artificial blood circulation according to an embodiment of the present invention may include a measuring unit (10) that measures EEG signals; an analog-to-digital converter (ADC) 20 that converts the EEG signals measured at the measuring unit 10 into digital signals; a control unit 50 that calculates EEG parameters from the digital EEG signals converted at the ADC 20, and calculates end-tidal carbon dioxide tension and cerebral blood flow from the EEG parameters.

The present application relates to an antibody drug conjugate containing phenanthroquinolizidine compound as shown in formula I, a pharmaceutical composition, a preparation method thereof, and the use thereof in preventing and / or treating diseases related to abnormal cell activity, including but not limited to preventing and / or treating tumor diseases. The antibody drug conjugate can achieve tumor enrichment, eliminate or reduce the toxic side effects caused by the action of phenanthroquinolizidine compound on non-disease tissues, and improve the therapeutic effect.

The invention discloses recombinant III-type collagen, hydrogel, a preparation method and application, and belongs to the technical field of medical materials. The protein has an amino acid sequence as shown in SEQ ID No.2 or 3, and has excellent biocompatibility and cell viability. The hydrogel based on the protein is formed by mixing a solution of the protein with a solution containing oxidized sodium alginate and hydroxypropyl methyl cellulose, adjusting the pH value, sequentially introducing an EDC / NHS cross-linking system and calcium ions, and standing. According to the process, a stable dual-network structure with a synergistic effect of an EDC / NHS catalyzed covalent cross-linked network and an OSA-Ca < 2 + > ionic cross-linked network is constructed. The obtained hydrogel has high mechanical strength, excellent toughness, lasting wet tissue adhesion and appropriate swelling property, can effectively adapt to complex stress changes of dynamic wounds, provides an active matrix for cells and promotes tissue repair.

This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a cyclic peptide toxin Amanitin derivative, its preparation method, and its application. Based on the natural Amanitin compound, glycine was replaced with alanine; simultaneously, the eighth amino acid was also replaced. The synthesized cyclic heptapeptide was sequentially oxidized, and proline, phenylalanine, dibutylisobutyric acid, and dihydroxyisoleucine were linked to design and synthesize a series of Amanitin derivatives, namely, products 1 to compounds 12 of this invention, which are 12 cyclic peptide toxin derivatives, and they exhibit good cellular activity.

The present application refers to photoswitchable chemical induced dimerization systems for reversible and repetitive control of cellular activities with light. Compounds, test systems, methods and uses are disclosed how the invention can be applied in the investigation of cellular processes. A photoswitchable compound consisting of: ligand A – linker A – photoswitch moiety – linker B – ligand B or ligand (photoswitch moiety) A – linker B – ligand B, wherein ligand A, ligand (photoswitch moiety) A and ligand B are ligands capable of binding a ligand binding domain of a first and a second protein. Linker A and linker B are as specified in the specification. The photoswitch moiety is of formula (I), formula (II), the cis-isomer thereof or of formula (II) wherein R1, R2, R3, R4 and A are as defined in the specification.

The invention provides application of a rice OsPDRA3 gene in improving insect resistance of rice. According to the invention, an OsPDRA3 gene (LOCOs01g42380) is cloned in a rice genome, and an SMART program is used for analyzing and predicting that the protein has multiple transmembrane domains and ATP enzyme structural domains (AAA < + >) related to various cell activities. The influence of OsPDRA3 on the tolerance of rice brown planthopper is further studied, and by comparing the tolerance of wild type and overexpressed OsPDRA3 transgenic plants to brown planthopper, the result shows that the survival rate of a rice line with overexpressed OsPDRA3 after being treated by brown planthopper is obviously increased compared with that of a wild type rice line (the survival rate is 0%), and reaches 75%-100%. Namely, it is shown that the OsPDRA3 gene can significantly improve the insect resistance of rice, can be widely applied to the fields of plant genetic engineering and plant disease resistance, and has huge economic value and application prospects.

An apparatus for generating a stream to treat a surface includes a base unit connected to a combined treatment unit (4, 14) including a body (4) defining a chamber to contain a liquid and discharge a stream of the liquid through the nozzle (14) toward the surface, and a manifold integrally formed together as a single piece with the body. The manifold is connected to a liquid supply conduit (42) to receive an inlet stream of the liquid and has a plurality of ports in communication with the chamber and configured for introducing the inlet stream into the chamber. The base unit includes an acoustic transducer positioned and configured to generate acoustic energy and to introduce the acoustic energy into the liquid contained in the chamber, and a casing (55) containing the acoustic transducer and having a mounting piece (52) engaged with the combined unit to releasably connect the combined unit to the base unit.

This invention belongs to the technical field of drug synthesis, specifically relating to adamantane derivatives, their synthetic methods, and applications. The adamantane derivatives described in this invention include intermediate structural formulas I, II, and III, as well as structures with the following general formula: Linker is a substituted or unsubstituted C6-C10 aryl group; R1 is hydrogen or a C1-C6 alkyl group; R2 is hydrogen, a C1-C6 alkyl group, or a nitrogen-containing or nitrogen-free structural fragment; or the overall structure of R1R2 is an N-substituted heterocyclopentyl or heterocyclohexyl group. The adamantane derivatives provided by this invention combine the adamantane structure with a portion of the OAB-14 group, altering the core structure and thus improving drug activity. This invention also provides a synthetic method for these derivatives. Through cellular activity studies, the resulting compounds are screened, demonstrating potential synergistic effects in the prevention of influenza and the treatment of Alzheimer's disease.

The present invention provides an antibody-ClpP agonist conjugate prepared using a ClpP agonist having a novel structure. The antibody-ClpP agonist conjugate has certain in vitro cellular activity.

Amino acid sequences capable of enhancing nuclear translocation are provided. Also referred to a nuclear localization signals (NLS) the sequences can be linked to or grafted into antibodies or fragments or fusion proteins thereof to enhance nuclear translocation of the antibody. Compositions and antibodies including an NLS conjugated or otherwise linked directly or indirectly to an active agent cargo are also provided. Exemplary cargo includes proteins, peptides, carbohydrates, polysaccharides, nucleic acid molecules, inorganic molecules, organic molecules, and diagnostic agents. Pharmaceutical compositions further including a pharmaceutically acceptable carrier are also provided. Methods of delivering the composition or antibody alone or with a cargo linked thereto to the nucleus of cell, methods of selecting or screening for compositions having a desired cellular activity, and methods of treating diseases and disorders are also provided.

This invention relates to the field of cellular drug screening technology, specifically to a genipin derivative, its synthesis method, and its uses. The genipin derivative is an N-substituted genipin lactam derivative or a cyclopentenepyridine derivative; the N-substituted genipin lactam derivative is a compound represented by general formula (I), and the cyclopentenepyridine derivative is a compound represented by general formula (II); wherein R is selected from any one of hydrogen, alkyl, phenyl, and aralkyl. This invention uses genipin as a lead compound, modifies the core structure, and performs cellular activity screening to identify lead compounds with good activity and low toxicity, providing a foundation for subsequent research on the anti-inflammatory effects of genipin.

Methods of synthesizing and screening nanoscale high-throughput chemical libraries for compounds that modulate cellular activity. In one aspect, is a synthesis and high-throughput screening method for a compound that affects at least one biological property in a biological assay comprising the steps of: performing a first reaction (R-I) in each well of a plurality of wells of a microplate to produce a different compound (C-I) in each well, wherein each well of the plurality of wells of the microplate comprises a different plurality of reactants and a solvent / s for the first reaction; optionally performing a second (R-II), third (R-III) and / or more reaction step in the wells; without purification of the reaction mixture, individually performing a biological assay with the contents of each well of the plurality of wells of the microplate; and assessing whether or not at least one compound in each well has a biological effect.

The present disclosure relates to bioactive conjugates, methods of making and uses thereof, in particular, the present disclosure relates to a novel class of bioactive conjugates obtained by improving the way the drug is conjugated to the targeting moiety in ADCs or SMDCs, methods of making and uses thereof in the preparation of treatments for diseases associated with abnormal cell activity.

The present application provides a drug-linker conjugate containing a protein degrader and an antibody-drug conjugate thereof. The present application also provides a preparation method for the drug-linker conjugate and the antibody-drug conjugate, as well as a use of the antibody-drug conjugate in the prevention and / or treatment of diseases associated with abnormal cellular activity, including but not limited to a use in the prevention and / or treatment of tumor diseases.

The present application provides a drug-linker conjugate containing an NMT inhibitor and an antibody-drug conjugate thereof. The present application also provides a preparation method for the drug-linker conjugate and the antibody-drug conjugate thereof, and use of the antibody-drug conjugate in preventing and / or treating diseases related to abnormal cell activity, including but not limited to use thereof in preventing and / or treating tumor diseases.