30 results about "Deoxycytidine" patented technology

The present invention relates to a pharmaceutical combination comprising a PARP inhibitor and a compound of formula (I), or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof, for use in a method of treating HR-functioning cancer, the pharmaceutical combination comprising a PARP inhibitor and a compound of formula (I): or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof;

Provided herein is an antisense oligonucleotide for targeting long non-coding RNA maternally expressed gene 3 (IncRNA Meg3), wherein the oligonucleotide comprises or consists of one of the following sequences in the 5' to 3' direction: (I) C G C dC dG dC dC dA dT dA dT dC dT C C C (SEQ I D NO: 1 ); (ii) C G G dA dC dA dA dA dA dC dT dG dG T T G (SEQ ID NO: 2); (ill) A A G dA dG dT dC dT dC dC dT dC dC dT T A A (SEQ ID NO: 3); (iv) G A T dT dA dG dC dC dC dT dG dT dG dT T C A (SEQ ID NO: 4); (v) C G G dC dA dC dA dA dG dA dG dC dC dA A A G (SEQ ID NO: 5); (vi) T O T dC dC dT dC dC dT dT dA dA dG dC C C C (SEQ ID NO: 6); or (vii) G T C dT dC dC dT dC dC dT dT dA dA dG C C C (SEQ ID NO: 7); wherein dA, dT, dG and dC are deoxyribonucleotides, or wherein dC is 5-methyl-2'-deoxycytidine; and wherein A, T, G and C are modified or unmodified nucleotide building blocks.

The present invention relates to a method for preparing 4′-thio-5-aza-2′-deoxycytidine which exhibits DNMT1 inhibitory activity. The production method according to the present invention can enhance reaction efficiency through efficient process development and can stereoselectively prepare 4′-thio-5-aza-2′-deoxycytidine, and thus is economical and appropriate for mass production.

The invention discloses an H-phosphonate solid-phase connexon, a preparation method thereof and application of the H-phosphonate solid-phase connexon in solid-phase flow synthesis of circular nucleic acid. According to the preparation method, a solid-phase synthesis technology is adopted, exposed amino resin and succinic anhydride are subjected to a condensation reaction to obtain a solid-phase carrier with carboxylic acid, then the solid-phase carrier and 5 '-O-(4, 4'-dimethoxytriphenylmethyl) deoxycytidine are subjected to an amidation reaction under the assistance of a condensing agent and a condensation activating agent, loading of deoxycytidine is achieved, and finally H-phosphonation of hydroxyl is completed. The H-phosphonate solid-phase linker is obtained. The linker disclosed by the invention can realize cyclization closure of a linear precursor by utilizing an efficient reaction between an H-phosphonate group and a terminal hydroxyl group of the linker. The synthesis strategy has the remarkable advantages that the cyclization process can be completed only in 6 hours, and the separation yield reaches up to 73%. The whole process condition is mild, the operation is simple and convenient, the reaction is rapid, and the gram-scale preparation of the cyclic nucleic acid can be efficiently realized.

The application discloses a transient transfection method for improving recombinant protein expression of CHO cells, and relates to the technical fields of eukaryotic cell gene transfection and animal cell culture. A cell suspension is obtained by mixing a CHO cell and a serum-free CHO cell basic culture medium; DNA and a transfection reagent are added into the cell suspension to mix a transfection culture, 5-azadeoxycytidine acid solution is added into the transfection culture at 0h-24h to form a transfection system and continue the transfection culture; the transfection system is added with a feeding culture medium at 1d-4d after the transfection culture to carry out suspension culture; the suspension culture is centrifuged at 7d to separate and harvest cell culture supernatant to complete recombinant protein expression. According to the application, 5-azadeoxycytidine acid is added into the transfection culture at a specific concentration, so that the expression of recombinant protein of the CHO cell is significantly improved during the transfection expression.

The invention relates to high-purity thymine, a process of purification of thymine, a process for preparing high-purity deoxythymidine, pharmaceutical compositions containing high-purity deoxythymidine and deoxycytidine as well as their use as pharmaceuticals for treatment of mitochondrial depletion syndromes in a mammal.

The invention discloses an enzyme composition, an immobilized enzyme and application. The enzyme composition consists of uridine phosphorylase and thymine phosphorylase. The enzyme composition and the immobilized enzyme are simple to prepare, have the characteristics of high conversion efficiency, high yield and simplicity and convenience in operation when being used for synthesizing 2 '-fluoro-2'-deoxycytidine, and can effectively reduce the production cost. Meanwhile, synthetic reaction conditions of the 2 '-fluoro-2'-deoxycytidine based on the enzyme composition and the immobilized enzyme are mild, green and environment-friendly, and the environmental problem caused by chemical synthesis can be avoided.

The invention discloses a siRNA molecule targeting a human SLC25A17 gene, the siRNA molecule comprises a positive-sense strand and an antisense strand, the specific sequence is as follows: the positive-sense strand: 5 '-CCUUGGAUGUGUUCAUCAUNn-3', the antisense strand: 5 '-AUGAUGAACACAUCAAGGNn-3', N in the positive-sense strand and N in the antisense strand are the same or different, and are respectively and independently cytosine C, uracil U, guanine G, adenine A, deoxycytosine dC, deoxyguanine dG, deoxyadenine dA or deoxythymine dT; n represents the number of N, and n = 0, 1 or 2. The invention further discloses application of the siRNA molecule of the targeted human SLC25A17 gene, and the siRNA molecule is applied to liver cancer treatment by efficiently inhibiting the expression level of SLC25A17.

The present invention relates to a compound of Formula (I): or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof, wherein X, W1, W2, Y, Z, R1, R2 and R3 are as defined in the disclosure herein, for use in therapy, particularly for use in the treatment of cancer. The present invention also relates to methods of treating cancer comprising the administration of a compound of Formula (I) to a subject in need thereof, and to pharmaceutical compositions and kits comprising such compounds.

The application discloses a kind of solid phase extraction-liquid quality connection simultaneously detecting multiple nucleotides in drinking water in the technical field of water pollution monitoring, first using solid phase extraction enrichment target material, nitrogen blow concentration, finally using the concentration of guanosine acid, adenosine acid, cytidine acid, uridine acid, deoxyguanosine acid, deoxyadenosine acid, deoxycytidine acid and deoxythymidine acid is determined using the multiple reaction monitoring mode of liquid chromatography tandem mass spectrometry, the present application combines solid phase extraction pretreatment technology with the detection technology of liquid chromatography tandem mass spectrometry, realizes the detection of trace nucleotide under complex matrix condition, the present application can realize the simultaneous determination of multiple nucleotides by one sample injection, with the advantages of high recovery rate, short detection time, many detection types and the like.

The application discloses a fluorescent probe based on rhodamine modified nucleoside and a preparation method and application thereof, and a structure formula of the fluorescent probe is as follows: the fluorescent probe is a novel fluorescent probe based on rhodamine modified nucleoside, is composed of rhodamine hydrazine-short-chain alkyne-2-deoxy cytidine, and has the advantages of high fluorescence intensity, good biological compatibility, good strong acid resistance, high sensitivity and good chemical stability. 3+ The fluorescent probe can be widely applied in the fields of in vivo and in vitro Fe detection, real-time monitoring of pH dynamics, preparation of pH test paper, cell imaging, construction of lysosome-targeting functional probes, design of in vivo contrast agents, treatment and diagnosis of gastrointestinal diseases and screening of related treatment drugs, and has great practical application value.

The invention relates generally to a pharmacological therapy for human genetic diseases, specifically those characterized by unbalance nucleotide pools, more specifically mitochondrial DNA depletion syndromes, and more specifically, thymidine kinase 2 (TK2) deficiency. The pharmacological therapy involves the administration of at least one deoxynucleoside, or mixtures thereof. For the treatment of TK2 deficiency, the pharmacological therapy involves the administration of either deoxythymidine (dT) or deoxycytidine (dC), or mixtures thereof. This administration of deoxynucleosides is applicable to other disorders of unbalanced nucleotide pools, especially those found in mitochondrial DNA depletion syndrome.

The invention discloses an EB virus related B cell lymphoma diagnostic kit based on GNAS methylation detection. The invention provides a new marker for diagnosis of EB virus related B cell lymphoma, provides a matched and verified special detection primer, and performs functional reverse verification of 5-aza-2 '-deoxycytidine drug intervention. According to the invention, the potential value of the marker in the aspect of curative effect prediction is defined, and a possible molecular basis is provided for implementing individualized demethylation treatment clinically.

The present disclosure provides pyrimidine nucleoside compounds, including torcitabine, thymidine, deoxyuridine, deoxycytidine and uridine, and methods to treat telomere biology disorders (TBDs) and aging-related diseases, including hematological disorder, liver disease, or hepatic fibrosis, comprising administering to a subject diagnosed with said telomere biology disorder a therapeutically effective amount of said compounds.

To provide a composition for use in the treatment of mitochondrial DNA depletion and / or multiple deletions syndrome.SOLUTION: Provided is a composition for use in the treatment of mitochondrial DNA depletion and / or deletion syndrome caused by a defect in DNA polymerase gamma subunit 1 (POLG1), the composition comprising more than one canonical deoxyribonucleoside selected from the group consisting of deoxyadenosine, deoxyguanosine, deoxycytidine, and deoxythymidine, wherein the deoxyribonucleosides are present in an equimolar ratio.SELECTED DRAWING: None

The present invention relates to a compound of Formula (I):or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof, wherein X, W1, W2, Y, Z, R1, R2 and R3 are as defined in the disclosure herein, for use in therapy, particularly for use in the treatment of cancer. The present invention also relates to methods of treating cancer comprising the administration of a compound of Formula (I) to asubject in need thereof, and to pharmaceutical compositions and kits comprising such compounds.

The present invention relates to a method for the generation of a cDNA library from transfer RNA (tRNA) comprising (a) optionally ligating at least one DNA adapter to 3′-end of tRNA, wherein 3′-end of the DNA adapter is preferably a chain terminator dideoxycytidine, preferably under one or more of the following conditions: (i) crowding reagent at 5% to 35%, preferably 15% to 30%, and most preferably about 25%, (ii) MgCl2 concentration of 1 mM to 15 mM, preferably 3 to 12 mM and most preferably about 10 mM (iii) a temperature of 12° C. to 37° C., preferably of about 25° C. (iv) a pH of 6.0 to 9.0, preferably 6.5 to 8.0 and most preferably about 7.0, (v) reducing agent concentration of 0.1 mM to 10 mM, preferably 0.5 to 5 mM and most preferably about 1 mM, and (vi) a reaction time of at least 30 min, preferably at least 1.5 h and most preferably at least 3 h; and (b) reverse transcription in a primer-dependent reaction, in case step (a) is present, or in a template-switching reaction, in case step (a) is absent, of tRNAs into cDNA by a group II intron reverse transcriptase, under the following conditions: (i) KCl or NaCl at a concentration of 20 mM to 250 mM, preferably 50 to 100 mM and most preferably about 75 mM, (ii) MgCl2 at a concentration of 0.5 mM to 15 mM, preferably 1 to 5 mM and most preferably about 3 mM, (iii) a temperature of 30° C. to 65° C., preferably of about 42° C., and (iv) a reaction time of at least 2 h, preferably at least 8 h and most preferably at least 15 h, and preferably (v) a pH of 6.5 to 9.5, preferably 7.0 to 8.5 and most preferably about 8.0, and / or (vi) a reducing agent (DTT) at a concentration of 1 mM to 12.5 mM, preferably 3 to 8 mM and most preferably about 5 mM.

The invention discloses a siRNA (small interfering Ribonucleic Acid) molecule of a targeted human SLC25A3 gene, which is composed of a positive-sense strand and an antisense strand, and the specific sequence of the siRNA molecule is as follows: the positive-sense strand is 5 '-AGUACAAGGCAUAUUUAANn-3', the antisense strand is 5 '-UUAAUUAUGUACUNn-3', or the positive-sense strand is 5 '-GACUCGUGAAGGAGUCNn-3', and the antisense strand is 5 '- Wherein N in the positive-sense strand and N in the antisense strand are the same or different and are respectively and independently cytosine C, uracil U, guanine G, adenine A, deoxycytosine dC, deoxyguanine dG, deoxyadenine dA or deoxythymine dT; n represents the number of N, and n = 0, 1 or 2. The invention further discloses application of the siRNA molecule of the targeted human SLC25A3 gene, and the siRNA molecule is applied to liver cancer treatment by efficiently inhibiting the expression level of the SLC25A3.

An oligonucleotide variant according to an embodiment of the present disclosure has a structure of Formula 1 may exhibit excellent in-vivo stability and anticancer effects:(N)x-[TGG]m[TTG][TGG]n-(M)y  [Formula 1]wherein, N and M are independently deoxyuridine (dU), deoxycytidine (dC), uridine (U), or cytidine (C), in which a halogen or hydroxy group is bound to 5- or 2′-position thereof; x and y are independently integers of 0 to 10 (except when x and y are simultaneously 0), n is an integer of 1 to 10; and m is an integer of 1 to 10.

The invention discloses a method for detecting iodo-nucleoside in drinking water through solid-phase extraction-vacuum centrifugal concentration-liquid chromatography-tandem mass spectrometry, which comprises the following steps: enriching target substances in the drinking water by using solid-phase extraction, and then concentrating a sample by using a vacuum centrifugal concentrator, and finally, determining the concentrations of 2-iodine adenosine, 8-iodine adenosine, 5-iodine cytidine, 8-iodine guanosine, 5-iodine uridine, 6-iodine uridine, 2-iodine-2 '-deoxyadenosine, 5'-iodine-5 '-deoxyadenosine, 5-iodine-2'-deoxycytidine, 5-iodine-2 '-deoxyuridine, 2'-iodine-2 '-deoxyuridine and 5'-iodine-5 '-deoxyguanosine by using a multi-reaction monitoring mode of liquid chromatography tandem mass spectrometry. According to the method disclosed by the invention, the detection technologies of solid-phase extraction, vacuum centrifugal concentration and high performance liquid chromatography-tandem mass spectrometry are combined, so that the detection of trace iodo-nucleoside under a complex matrix condition is realized; the method has the advantages of low detection limit, high sensitivity, short detection time and the like.

(3R, 4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H- chromen-7-ol (TRX-E-002-1) for use in a method of treatment for a hematological cancer being acute myeloid leukemia or multiple myeloma in a subject in need thereof, the method comprising administering to the subject an effective amount of TRX-E-002-1. The method may further comprise administering to the subject an effective amount of a second compound selected from the group consisting of (i) a BCL-2 inhibitor such as venetoclax, navitoclax or obatoclax, (ii) a deoxycytidine analogue chemotherapeutic such as cytarabine or gemcitabine, (iii) a hypomethylating agent such as azacitidine or decitabine, (iv) an anthracycline chemotherapeutic such as daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin or mitoxantrone, (v) a proteasome inhibitor such as carfilzomib, bortezomib, and ixazomib, (vi) an immunomodulatory drug such as pomalidomide, lenalidomide, and thalidomide and(vii) a corticosteroid drug such as dexamethasone or prednisone, and (viii) an alkylator such as bendamustine, cyclophosphamide, melphalan, and melflufen. Corresponding combination pharmaceutical compositions.

The invention discloses a near-infrared response copper sulfide nano-composite as well as a preparation method and application thereof, and belongs to the technical field of nano-drugs. The invention relates to a near-infrared response copper sulfide nano composite, which comprises CuS nano particles, 2 ', 2'-difluorodeoxycytidine (GEM), polyethyleneimine (PEI) and folic acid (FA), cuS nanoparticles are used as a carrier, 2 ', 2'-difluorodeoxycytidine (GEM) is carried on the CuS nanoparticles to form a structural main body, polyethyleneimine (PEI) is used for modifying the structural main body, and folic acid (FA) is used as a tumor cell targeting agent and is modified on the surface of the structural main body. The nano compound integrates chemotherapy / PTT / CDT and a copper death effect, so that multi-mode combined anti-tumor treatment is realized, and an innovative solution is provided for anti-tumor treatment.

The invention relates to the technical field of medicines, and provides application of zalcitabine in drugs for inhibiting and / or preventing and / or relieving and / or treating multiple myeloma in order to solve the problems that whether zalcitabine has anti-tumor activity in MM and related molecular mechanisms are not clear at present. The invention relates to a pharmaceutical preparation for inhibiting and / or preventing and / or relieving and / or treating multiple myeloma. The pharmaceutical preparation comprises an active ingredient and a pharmaceutically acceptable excipient, wherein the active ingredient is 2 ', 3'-dideoxycytidine. Researches show that zalcitabine induces mitochondrial dysfunction by targeted inhibition of expression of TFAM, and induces occurrence of ferroptosis of MM cells by triggering a cGAS-STING pathway through mtDNA cytoplasm stress. In-vivo animal experiments further show that zalcitabine can significantly slow down tumor growth. In addition, the antineoplastic activity of zalcitabine is also verified in a bone marrow sample derived from an MM patient.

The present application relates to a series of 2'-deoxy-2',2'-difluoro cytidine (2',2'-difluoro 2'-deoxycytidine, dFdC, gemcitabine) Protide and antibody specific to tumor antigen form conjugates and its preparation method and application in the field of treatment. Further, the present application provides a series of antibody-linker-2'-deoxy-2',2'-difluoro cytidine Protide conjugate to form antibody drug conjugate (ADC). The structural features are mainly in the 5'-phosphate phenylamide amino acid ester corresponding group in the structure of 2'-deoxy-2',2'-difluoro cytidine and the linker for linkage, and then coupled with the corresponding tumor specific antibody to form ADC. These ADCs target antigens on tumor cells, endocytose into tumor cells, release the drug 2'-deoxy-2',2'-difluoro cytidine monophosphate, kill tumor cells, and cause tumor cell apoptosis.

To provide deoxycytidine compositions with reduced residual solvent content.SOLUTION: Provided is a composition comprising Form B deoxycytidine and at least one residual solvent, the form B deoxycytidine being characterized by a powder X-ray diffraction pattern comprising peaks at 13.7°, 17.2°, 18.0°, 19.2° and 22.8 (2θ) (± 0.2°(2θ)), the at least one residual solvent being selected from the group consisting of methanol, toluene, methylene chloride, ethanol, tert-butylmethyl ether, acetone, ethyl acetate, and n-heptane, and the composition being stable for at least 3 months at 25±2°C and 60±5% relative humidity.SELECTED DRAWING: None

The present invention relates to a method for preparing 4'-thio-5-aza-2'-deoxycytidine which exhibits DNMT1 inhibitory activity. The production method according to the present invention can enhance reaction efficiency through efficient process development and can stereoselectively prepare 4'-thio-5-aza-2'-deoxycytidine, and thus is economical and appropriate for mass production.

The invention discloses deoxycytidine monophosphate hydroxylase AfhB and application of the deoxycytidine monophosphate hydroxylase AfhB. The dCMP hydroxylase AfhB obtained by screening from the genome of the bacteriophage HY126 can be used for green synthesis or fermentation production of 5hdCMP, so that the environmental pollution caused by a traditional chemical synthesis method is greatly reduced, and a new enzyme element and way are provided for development of a gene editing technology and fermentation production of 5hdCMP and derivatives thereof in industrial fermentation.

Provided herein are polymorphic forms of deoxycytidine and methods for preparing same. Also provided are compositions comprising polymorphic forms of deoxycytidine and at least one residual solvent, and methods for treating mitochondrial diseases using the compositions.

The invention discloses a siRNA molecule of a targeted human ANKRD10 gene, the siRNA molecule is composed of a positive-sense strand and an antisense strand, and the specific sequence of the siRNA molecule is as follows: the positive-sense strand is 5 '-GGAGUUUGCUGUUGUAACANn-3', and the antisense strand is 5 '-UGUUACAACAUCCNn-3'; wherein N in the positive-sense strand and N in the antisense strand are the same or different and are respectively and independently cytosine C, uracil U, guanine G, adenine A, deoxycytosine dC, deoxyguanine dG, deoxyadenine dA or deoxythymine dT; n represents the number of N, and n = 0, 1 or 2. The invention further discloses application of the siRNA molecule of the targeted human ANKRD10 gene, and the siRNA molecule is applied to liver cancer treatment by efficiently inhibiting the expression level of ANKRD10.