44 results about "Topoisomerase" patented technology

An antigen-binding molecule that binds to a target antigen, comprising (i) a target antigen-binding moiety, and (ii) at least one linker-payload moiety, wherein the antigen-binding molecule comprises (a) DNA damage response (DDR) inhibitor moiety, and (b) a DNA topoisomerase I (TOP1) inhibitor moiety.

An antigen-binding molecule that binds to HER2, comprising (i) a HER2-binding moiety, and (ii) at least one linker-payload moiety, wherein the antigen-binding molecule comprises (a) DNA damage response (DDR) inhibitor moiety, and (b) a DNA topoisomerase I (TOP1) inhibitor moiety.

The invention provides heterobifunctional compounds comprising an effector protein binding moiety selected from mTor, PLK1, CDKI, CDK2, CDK9, BRD4, AURKA, AURKB, MEK, Src, c-KIT, KIF11, HSP90, tubulin, proteasome, topoisomerase or HD AC which is linked to a moiety that binds to a target protein selected from KRAS, HER2 or EGFR. Pharmaceutical compositions and their use in treating disease, such as cancer, are also disclosed.

The present invention relates to an alcohol and amine-containing avixetecan derivative, and pharmaceutically acceptable salts or solvates thereof, comprising a structure of formula (I): wherein X is as defined in the disclosure. The disclosure also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of cancer and / or tumors. # imgabs0 #

The present invention relates to the use of small molecule compounds that allosterically inhibit ALC1 (CHD1L), in particular two classes allosteric inhibitors of ALC1 (CHD1L), of Formula (I) and Formula (II), that show a potentiating, preferably additive effect in the treatment of proliferative disease when combined with several classes of cancer drugs, namely inhibitors of Topoisomerase I, Topoisomerase II, ATM, ATR, Wee1, BRD, and MEK, or when combined with mitomycin C, paclitaxel, with ionizing radiation, or with an antibody drug conjugate with a tumor specific antibody conjugated to a TOP1 inhibitor. Furthermore, the present invention relates to said inhibitors of ALC1 of Formula (II) that show a synergistic effect in the treatment of pancreatic cancer or fallopian tube cancer when combined with a PARP inhibitor (Poly(ADP-ribose)-Polymerase inhibitor (PARPi)). By being synergistic with the function of said cancer drugs, said ALC1 inhibitors, in particular those of Formula (I) and Formula (II), potentiate the cancer cell killing properties of the aforementioned cancer drugs, in particular enabling therapeutic approaches where any of the aforementioned inhibitors is already used as part of the standard of care.

The invention provides a compound as shown in a formula (I), and a stereoisomer, a tautomer, an isotope label, nitrogen oxide, a solvate, a polymorphic substance, a metabolite, ester, pharmaceutically acceptable salt or prodrug thereof, or a pharmaceutical composition thereof, which have better antibacterial and anti-inflammatory effects, can be used as an antibiotic, and can be used for preparing a pharmaceutical preparation for preventing and treating diseases. The compound can treat infection caused by pathogenic microorganisms resistant to erythromycin and telithromycin, and simultaneously acts on double targets of ribosome and topoisomerase.

The invention belongs to the technical field of medical chemistry, and discloses a 5-O-carbon mould amine tylosin lactone derivative with a double-target combined antibacterial effect as well as a preparation method and application of the 5-O-carbon mould amine tylosin lactone derivative. The derivative is a compound as shown in a formula I, and pharmaceutically acceptable salt, eutectic, tautomer, polymorphic substance, solvate, prodrug or isotope labeled compound thereof. The compound can act on a bacterial ribosome 50S subunit and DNA topoisomerase IV at the same time, and shows an excellent antibacterial effect in an antibacterial activity test, and the minimum inhibitory concentration (MIC) reaches 0.0625 mu g / mL. The compound has the advantages of being high in antibacterial activity, wide in antibacterial spectrum and capable of achieving rapid sterilization, and a new choice is provided for developing drugs with antibacterial activity.

The invention discloses an application of mitochondrial topoisomerase I or a coding gene thereof, relates to the technical field of biological medicines, and particularly provides an application of the mitochondrial topoisomerase I or the coding gene thereof as a therapeutic target in screening or preparing a medicine for treating Alzheimer's disease. The action mechanism of the mitochondrial topoisomerase I in the Alzheimer's disease is fully explored, it is found that deletion of the coding gene of the mitochondrial topoisomerase I can cause increase of APP and A beta levels and finally cause learning and memory impairment similar to the Alzheimer's disease, and the mitochondrial topoisomerase I can be used as a potential target for treatment of the Alzheimer's disease and can be used for treating the Alzheimer's disease. The overexpressed mitochondrial topoisomerase I can significantly reduce APP and A beta levels and treat the Alzheimer's disease.

The present invention provides a topoisomerase I / II dual-target inhibitor, its preparation method, and application, belonging to the field of medicine. The present invention uses 6-bromopiperonal as a raw material to synthesize a compound having a structural formula as shown in Formula I. This compound is a novel topoisomerase I / II dual-target inhibitor that can be used to treat diseases such as small cell lung cancer, advanced metastatic ovarian cancer, advanced breast cancer, colorectal cancer, and bladder cancer, and has good application prospects.

The present invention relates to: an active camptothecin derivative (a) represented by Formula 1 designed so as to bind to a DDX5 protein and an E3 ligase; a prodrug (b) thereof, preferably an antibody-drug conjugate (ADC) thereof, designed so as to release the active camptothecin derivative (a) at a target site in vivo; the active camptothecin derivative (a) or the FL118 compound shown in the formula 2 is connected with a complex (c) containing a target DDX5 protein ligand through a joint, so that the 1-type topoisomerase inhibition capability in the active camptothecin derivative (a) or the FL118 compound shown in the formula 2 is inactivated. The active camptothecin derivative designed according to the present invention can bind to DDX5 protein in cells and induce cell death by degradation of the DDX5 protein.

This invention discloses a method for rice to withstand heat stress. RMI1 Genes and their applications. Among them... RMI1 The nucleotide sequence of the gene is shown in SEQ ID No. 1, and the amino acid sequence of the protein it encodes is shown in SEQ ID No. 2; this invention verifies RMI1 The function of the gene, RMI1 protein is located in the cell nucleus, rmi1-1 In mutants RMI1 The deletion of 33 base pairs in the gene results in the loss of 11 amino acids in the RMI1-1 protein, making... rmi1-1 High temperatures during the seedling stage cause a large number of abnormal chromosomes to adhere and fragment during the late mitotic phase of root tip cells, resulting in stunted plant growth and development. rmi1-1 High temperatures during the reproductive growth period of plants lead to a large number of chromosome fragments and adhesions in the late stage of meiosis I, resulting in sterility; high temperatures also affect the interaction between RMI1-1 protein and topoisomerase TOP3α and helicase RECQ4. rmi1-cr3 Frameshift mutations lead to abnormal embryo and endosperm development; overexpression RMI1 This invention can enhance the heat resistance of rice. RMI1 The analysis of gene function provides genetic resources for the breeding of heat-resistant rice varieties.

The invention discloses a recombinant topoisomerase and an application of the recombinant topoisomerase in plasmid linearization. The invention discloses a recombinant topoisomerase with an amino acid sequence as shown in SEQ ID NO.1 at first. The invention further discloses an application of the recombinant topoisomerase in plasmid linearization. The recombinant topoisomerase does not depend on recognition of a specific DNA sequence, cutting sites can be formed on plasmids in a super-spiral form, then a linear product is obtained through the cutting effect of T7 endonuclease I, and linearization of plasmids with unknown sequences can be achieved. The plasmid linearization kit developed by using the recombinant topoisomerase has the characteristics of rapidness, high efficiency and wide applicability, and can realize full-length sequencing of unknown plasmids by combining with a three-generation sequencing technology.

The invention relates to the technical field of medicinal chemistry, and further discloses a folium eriobotryae extract, a preparation method of the folium eriobotryae extract and application of the folium eriobotryae extract in preparation of a medicine with an anti-breast cancer effect. The preparation method of the folium eriobotryae extract comprises the following steps: taking folium eriobotryae, adding the folium eriobotryae into an ethanol aqueous solution according to a material-liquid ratio of 1g: (80-120mL), carrying out ultrasonic extraction, separating an extracting solution after the extraction is finished, and concentrating and drying to obtain the folium eriobotryae ultrasonic extract; and taking the folium eriobotryae ultrasonic extract to obtain the folium eriobotryae extract. Researches show that the loquat leaf extract prepared by the method disclosed by the invention has an inhibition effect on topoisomerase I. Therefore, the folium eriobotryae extract has potential application value when being used for preparing the medicine with the anti-breast cancer effect.

The disclosure relates to methods of attaching a nucleic acid adapter to a target polynucleotide, and methods of preparing a nucleic acid library, using a topoisomerase activated adapter. The disclosure also relates to methods of producing adapted PCR amplicons, and kits for carrying out the methods of the disclosure.

The present disclosure provides covalent-induced drug conjugates comprising a KRASG12C binding moiety and a topoisomerase 1 payload moiety, as well as compositions and methods of use thereof.

The application discloses a kind of bionic composite nanomedicine and its preparation method and application, which is composed of platelet membrane, chemotherapeutic drug DX8951f and topoisomerase II siRNA;The chemotherapeutic drug DX8951f and topoisomerase II siRNA are self-assembled to form composite nanoparticles by electrostatic interaction, and the platelet membrane is coated on the surface of the composite nanoparticles.The application successfully constructs a kind of platelet membrane coated DX8951f and topoisomerase II siRNA carrier-free bionic nanomedicine for the first time, overcomes DX8951f clinical drug resistance problem through chemotherapy-gene synergistic effect, realizes the stable bionic modification of carrier-free nanoparticles by mechanical extrusion coating process, significantly improves the in-vivo stability, tumor targeting and biological safety of drug.

This invention relates to the use of small molecule compounds that allosterically inhibit ALC1 (CHD1L), particularly two classes of ALC1 (CHD1L) allosteric inhibitors of formulas (I) and (II). When combined with inhibitors of several classes of cancer drugs, namely topoisomerase I, topoisomerase II, ATM, ATR, Wee1, BRD, and MEK, or when combined with mitomycin C, paclitaxel, ionizing radiation, or antibody-drug conjugates having tumor-specific antibodies conjugated to TOP1 inhibitors, the small molecule compounds and the allosteric inhibitors exhibit enhancing, preferably additive, effects in the treatment of proliferative diseases. Furthermore, this invention relates to the ALC1 inhibitor of formula (II), which, when combined with PARP inhibitors (poly(ADP-ribose)-polymerase inhibitors (PARPi)), exhibit synergistic effects in the treatment of pancreatic cancer or fallopian tube cancer. By synergizing with the functions of the aforementioned cancer drugs, the ALC1 inhibitors, particularly those of formulas (I) and (II) that enhance the cancer cell killing properties of the aforementioned cancer drugs, are particularly capable of achieving treatments in which any of the aforementioned inhibitors have already been used as part of standard care.

The expression of the ATXN2 gene can be modulated to reduce the amount of ataxin-2 protein produced by a cell. This can be accomplished by administering to the cell an effective amount of an ATXN2 modulating agent. Screening was performed with 428,749 compounds for lowering expression of an ATXN2-luciferase reporter in HEK-293 cells, with a multiplexed cell viability assay to ensure target reduction in the absence of cytotoxicity. Secondary qHTS assays included a CMV-luciferase reporter expressed in HEK-293 cells as well as a biochemical assay using recombinant luciferase to detect inhibitors of the reporter enzyme. A diverse set of compounds were found to reduce ATXN2 expression, including compounds targeting HSP90, cardiac glycosides, NaK-ATPases and topoisomerases.

The present invention relates to a method for determining whether a sample comprises a pathogen or not, such as for determining whether a subject is likely to be infected with a pathogen, said pathogen expressing DNA modifying enzymes capable of cleaving and ligating DNA, such as topoisomerases and integrases. The invention also relates to kits of parts for performing such methods and uses thereof.

The application discloses a kind of bionic composite nanomedicine and its preparation method and application, which is composed of platelet membrane, chemotherapeutic drug DX8951f And topoisomerase II siRNA;The chemotherapeutic drug DX8951f With topoisomerase II siRNA self-assemble to form composite nanoparticles by electrostatic interaction, and the platelet membrane is coated on the surface of the composite nanoparticles.The application successfully constructs a kind of platelet membrane coated DX8951f With topoisomerase II siRNA The carrier-free bionic nanomedicine, overcomes DX8951f Clinical drug resistance problem by chemotherapy-gene synergistic effect, realizes the stable bionic modification of carrier-free nanoparticle by mechanical extrusion coating process, significantly improves drug in-vivo stability, tumor targeting and biological safety.

The present invention relates to (a) an active camptothecin derivative represented by Chemical Formula 1 below, which is designed to bind to the DDX5 protein and an E3 ligase; (b) a prodrug thereof designed to release the active camptothecin derivative (a) at an in vivo target site; or (c) a ligand-containing complex targeting the DDX5 protein, in which an topoisomerase-1 inhibitory ability of the active camptothecin derivative (a) or FL118 compound of Chemical Formula 2 is inactivated through linker conjugation. The active camptothecin derivative designed according to the present invention may bind to the DDX5 protein in cells to induce cell death through DDX5 protein degradation.

The invention relates to the technical field of films, in particular to a preparation method of a polylactic acid antibacterial film. The polylactic acid antibacterial film is prepared from the following raw materials in parts by weight: 80-95 parts of a polylactic acid base material, 3-10 parts of a first antibacterial material, 2-8 parts of a second antibacterial material, 4-12 parts of a first reinforcing material, 2-5 parts of a second reinforcing material and 1-3 parts of a dispersing aid. According to the preparation method, phenolic acid molecules penetrate through microbial cell membranes through a hydrophobic effect to destroy membrane integrity, flavone components are combined with bacterial DNA topoisomerase to inhibit nucleic acid replication, and the two substances generate a synergistic effect through a pi-pi conjugation effect, so that the antibacterial performance of the polylactic acid film can be remarkably improved; in addition, kudzuvine root polysaccharide and konjac glucomannan form a slow-release layer on the surface of the film, antibacterial components are gradually released through hydrogen bonds, the antibacterial performance of the film can be kept for a long time, and the problem that a traditional antibacterial agent is prone to migration and failure is solved.

The present invention belongs to the technical field of chemical pharmaceuticals, and particularly relates to anti-tumor drugs. Specifically, it relates to an evodiamine derivative, a rutaecarpine derivative, and their preparation methods and applications. The present invention provides an evodiamine derivative and a rutaecarpine derivative with higher anti-tumor activity in vitro and in vivo. By introducing a new drug fragment at the N-13 position of the B ring of evodiamine or rutaecarpine for structural modification, and using an acyl aniline group to replace the hydrogen atom on the imino group of the B ring of evodiamine / rutaecarpine, a series of novel small molecule evodiamine derivatives and small molecule rutaecarpine derivatives that target and inhibit DNA topoisomerase are obtained. The study of anti-tumor activity in vitro shows that this type of molecule described in the present invention has strong inhibitory activity against tumor cell lines and can promote the apoptosis of tumor cells.

The present disclosure relates to a method of treating malignant fungating wound (MFW) and / or the signs and symptoms of MFW in a subject in need thereof, by administering an inhibitor of DNA gyrase and / or topoisomerase and / or MD2-TLR interaction to the wound. The DNA gyrase and / or topoisomerase and / or MD2-TLR inhibitor is preferably, but not limited to, besifloxacin. It is found that the DNA gyrase and / or topoisomerase and / or MD2-TLR inhibitor results in effective neutralization / reduction of aerobic and anaerobic bacteria found in MFW site. When administered to the wound topically and / or intralesionally, the DNA gyrase and / or topoisomerase and / or MD2-TLR inhibitor, reduces malodor and pain associated with the MFW and improves quality of life. The present disclosure also relates to a pharmaceutical composition comprising a DNA gyrase and / or topoisomerase and / or MD2-TLR inhibitor, such as, besifloxacin, and a pharmaceutically acceptable excipient as well as use of these compositions in treating the signs and symptoms of MFW.

The present invention relates to (a) an active camptothecin derivative represented by Chemical Formula 1, which is designed to bind to DDX5 protein and E3 ligase; (b) a prodrug thereof, preferably an antibody-drug conjugate (ADC) thereof, which is designed to release the active camptothecin derivative (a) at a target site in vivo; or (c) a complex containing a DDX5 protein-targeting ligand, in which the ability of the active camptothecin derivative (a) or an FL118 compound of Chemical Formula 2 to inhibit type 1 topoisomerase is inactivated through a linker connection.The active camptothecin derivative designed according to the present invention can bind to DDX5 protein in cells to induce cell death through DDX5 protein degradation.

The present invention relates to the use of m-AMSA or its derivatives or their pharmaceutically acceptable salts in the preparation of drugs for preventing and / or treating African swine fever virus infection, and in the preparation of drugs for inhibiting the activity of African swine fever virus topoisomerase. The present invention first discovered and confirmed through experiments that m-AMSA can completely inhibit the activity of pP1192R to relax supercoiled DNA, and can effectively reduce the viral titer of African swine fever virus in porcine alveolar macrophages, and its viral inhibition rate can be as high as 98.56% after 48 hours of administration at the highest dosage. The above results show that the small molecule compound m-AMSA or its derivatives or their pharmaceutically acceptable salts have great potential clinical application value in treating or preventing ASFV infection.

The disclosure provides novel topoisomerases which exhibit weakened ability to form a covalent bond to the 5′-(C / T)CCTT-3′recognition site in the presence of increased NaCl concentrations relative to wild-type, together with novel methods for synthesizing DNA in the 3′ to 5′ direction using the novel topoisomerase; and other compounds, compositions, methods and devices comprising or utilizing topoisomerases which exhibit reduced covalent bond formation to the 5′-(C / T)CCTT-3′ recognition site in the presence of increased NaCl concentrations, relative to wild-type.

The invention discloses an intelligent algorithm drug delivery system based on ferroptosis synergetic chemotherapy and a preparation method thereof.The drug delivery system comprises a microneedle serving as a carrier and a therapeutic active ingredient loaded in the carrier, and the drug delivery system and adriamycin-mediated chemotherapy pathway act synergistically through a GFD-mediated ferroptosis pathway; the total drug loading capacity of the microneedle carrier is calculated according to the postoperative residual cavity volume of a patient and the individual metabolic factors of the patient, and the expected treatment cycle of the drug delivery system is calculated according to the total drug loading capacity and the daily degradation release rate based on the age of the patient. The intelligent algorithm drug delivery system is personalized in form, computable in dosage, intelligent in release and synergetic in treatment. The activity of the GFD mimic enzyme relieves hypoxia and induces ferroptosis of tumor cells; inducing cell apoptosis mediated by topoisomerase II by using DOX; and the two can synergistically form a'ferroptosis-apoptosis' dual-channel to kill tumor cells and reverse the drug resistance of tumor chemotherapy.

The application discloses a method for synthesizing a structure monomer of a topological protein in a cell-free system, comprising the following steps: synthesizing a basic sequence comprising a gene sequence for expressing a target protein, a gene sequence for expressing SpyTag or a gene sequence for expressing SpyCatcher; and adding the basic sequence into a cell-free system to synthesize the structure monomer comprising the target protein. The application also provides a method for synthesizing a topological protein in a cell-free system. The purpose of the application is to provide a method for synthesizing a protein which is simpler and faster than a cell system, has an unprecedented design freedom in an open environment, and is controllable in polymerization degree and length of the synthesized protein.

The invention discloses an application of a reagent for detecting biomarker topoisomerase TOP1 expression in preparation of a product for diagnosis or prognosis of a head and neck cancer object, an application of TOP1 as a target in screening of a medicine for treating head and neck cancer, and an application of a TOP1 expression inhibitor in preparation of a medicine for treating head and neck cancer. The invention provides a new marker and a therapeutic target TOP1 for diagnosis and prognosis of the head and neck cancer, and provides a new reference for a precise tumor treatment scheme; a certain reference value is provided for further subsequent exploration of the specific action mechanism of TOP1 for promoting HNSCC cell functions, and a new thought is provided for research of head and neck cancer pathogenesis and treatment strategies.