45 results about "Ribonucleotide reductase" patented technology

The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E. coli TrxR with Ki of 0.14 μM and 0.46 μM, respectively. E. coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains. Two major pathogenic bacteria, which previously had not been known to be sensitive to ebselen, Mycobacterium tuberculosis (tuberculosis) and Helicobacter pylori (stomach ulcer and cancer), were shown to be excellent targets. Helicobacter pylori was also sensitive to ebsulfur.

The present invention provides a recombinant HSV having the ability to specifically kill tumor cells such as human glioma cells in vivo, useful and safe for treating human glioma, etc. and that can easily put to clinical use. A new recombinant HSV, KeM345, is constructed by inserting a γ34.5 gene transcription unit, which is expressed by Musashi1 promoter, into a ribonucleotide reductase gene site of the genome of a herpes simplex virus (HSV) previously attenuated, by means of homologous recombination and obtained as a purified strain. Since KeM345 is a recombinant virus itself, it can not only induce viral proliferation by being transmitted to culture cells but can also induce viral replication equivalent to that of wild-type HSV, showing an excellent cytotoxic effect (cytolytic ability) selectively upon a malignant glioma.

The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E. coli TrxR with Ki of 0.14 μM and 0.46 μM, respectively. E. coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains. Two major pathogenic bacteria, which previously had not been known to be sensitive to ebselen, Mycobacterium tuberculosis (tuberculosis) and Helicobacter pylori (stomach ulcer and cancer), were shown to be excellent targets. Helicobacter pylori was also sensitive to ebsulfur.

Provided are: a novel sulfonamide compound having ribonucleotide reductase inhibitory activity or a salt thereof; and a pharmaceutical composition which contains this sulfonamide compound or a salt thereof as an active ingredient. A compound represented by formula (I) or a salt thereof. (In the formula, X1 represents an oxygen atom or the like; X2 represents an oxygen atom; X3 represents -NH-; X4represents a hydrogen atom or the like; R1 represents -C(R11)(R12)- or the like; R11 and R12 may be the same or different and each represents a hydrogen atom or the like; R2 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R3 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; and R4 represents a hydrogen atom or the like.)

The present invention provides a novel sulfonamide compound having a ribonucleotide reductase inhibitory activity or a salt thereof, and a pharmaceutical composition containing the same as an active ingredient.A compound represented by Formula (I) [wherein, X1 represents an oxygen atom or the like; X2 represents an oxygen atom; X3 represents —NH—; X4 represents a hydrogen atom or the like; R1 represents —C(R11)(R12)— or the like; R11 and R12 are the same or different and each represents a hydrogen atom or the like; R2 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R3 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R4 represents a hydrogen atom or the like] or a salt thereof.

Various genes of herpes virus of turkeys (HVT), Marek's disease virus (MDV) and infectious laryngotracheitis virus (ILTV) have been identified as non-essential regions (and candidates for insertion sites for foreign genes) and / or as antigen-encoding regions. The former include the HVT homologue of the HSV (herpes simplex virus) gC gene, the TK (thymidine kinase) region of MDV or ILTV, ORF3 of ILTV (as defined herein), the ribonucleotide reductase (large subunit) gene of ILTV, MDV or HVT and the ribonucleotide reductase (small subunit) gene of MDV. The antigen-encoding regions include the HVT homologues of the HSV gB, gC and gH genes, the ILTV homologue of HSV gB, ORF2 of ILTV, and the HVT homologue of the HSV-1 immediate early genes IE-175 and IE-68. Manipulation of these genes allows vaccines to be prepared comprising attenuated virus or virus carrying heterologous antigen-encoding sequences.