Disease relevance of Riboxamide

• Resistance of cultured Lewis lung carcinoma cell lines to tiazofurin [1].
• Relationships between the cytotoxicity of tiazofurin and its metabolism by cultured human lung cancer cells [2].
• Tiazofurin induction of mouse erythroleukemia cell hemoglobin production in the absence of commitment or changes in protooncogene expression [3].
• Reported here are three aspects of tiazofurin induction of myeloid differentiation in HL60 human acute promyelocytic leukemia cells [4].
• Sixteen consecutive patients with end stage acute nonlymphocytic leukemia or myeloid blast crisis of chronic granulocytic leukemia were treated with tiazofurin [5].

Psychiatry related information on Riboxamide

• The possible relevance to the biochemical basis of paranoid schizophrenia which occurs reversibly after high-dose acivicin or tiazofurin treatment was discussed [6].
• The effects of tiazofurin on basal and amphetamine-induced motor activity in rats [7].

High impact information on Riboxamide

• Nicotinamide riboside kinases from yeast and humans essential for this pathway were identified and found to be highly specific for phosphorylation of nicotinamide riboside and the cancer drug tiazofurin [8].
• The results demonstrate the spontaneous emergence of resistance from a tiazofurin-sensitive cell line [1].
• If similar processes occur during adaptation of human tumor cells to culture, this may explain the finding of low activity of tiazofurin toward a range of human tumor cell lines [1].
• Flow cytometry studies indicated that tiazofurin selectively depleted the LLAK cell population of S- and G2-phase cells [1].
• Incubation of L1210 cells with 10 microM tiazofurin or selenazofurin resulted in inhibition of cell growth, reduction of cellular NAD content, and interference with NAD synthesis [9].

Chemical compound and disease context of Riboxamide

• Modulation of the guanylate pathway in glioblastoma by inhibition of IMP dehydrogenase with tumor specific agents such as tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) appears to be a rational therapeutic approach [10].
• In patients with chronic granulocytic leukemia in blast crisis, daily tiazofurin infusions decreased the high IMP DH activity in blast cells and resulted in 77% response (G. Weber. In: R. A. Harkness et al., Purine and Pyrimidine Metabolism in Man, Vol. VII, Part B, pp. 287-292, 1991) [11].
• This indicates that PLC beta 1 down-regulation is tightly linked with erythroid differentiation of Friend erythroleukemia cells and that the autonomous nuclear signaling via inositol lipid cycle can be controlled by the antitumor drug tiazofurin [12].
• The inhibitory mechanisms of ribavirin 5'-monophosphate (RMP) and thiazole-4-carboxamide adenine dinucleotide (TAD), the active forms of the antimetabolites ribavirin and tiazofurin, were investigated in IMP dehydrogenase purified to homogeneity from rat hepatoma 3924A [13].
• Combinations of selenazofurin and tiazofurin had additive effects against Japanese encephalitis, yellow fever, and Korean hemorrhagic fever viruses [14].

Biological context of Riboxamide

• Down-regulation of the c-ras gene appears to be part of the complex process associated with tiazofurin-induced erythroid differentiation and relates to the perturbations of GTP metabolism [15].
• Induction of erythroid differentiation and modulation of gene expression by tiazofurin in K-562 leukemia cells [15].
• Tiazofurin-mediated cell differentiation is a multistep process [15].
• Sequential incubation of HL-60 cells with trimidox (25 mumol/L) for 24 hours and then with 10 mumol/L tiazofurin (an inhibitor of inosine monophosphate dehydrogenase) for 4 days produced synergistic growth inhibitory activity, and the cell number decreased to 16% of untreated controls [16].
• This study demonstrates that treatment of HL-60 cells with tiazofurin is associated with a fourfold increase in membrane binding sites for the nonhydrolyzable analogue GDP beta S [17].

Anatomical context of Riboxamide

• Induction of HL60 cell differentiation by tiazofurin and its analogues: characterization and efficacy [4].
• Biochemical consequences of resistance to tiazofurin in human myelogenous leukemic K562 cells [18].
• The present study showed that the tiazofurin-induced depression of IMP DH activity in rat bone marrow can be maintained by ribavirin injection [11].
• Tiazofurin phosphorylating activity from CHO cell extracts was resolved into two peaks by DEAE-cellulose chromatography [19].
• Tiazofurin was readily detectable in both plasma and cerebrospinal fluid within 20 min of commencement and for 24 h after a short i.v. infusion of the drug [20].

Associations of Riboxamide with other chemical compounds

• Second, HL60 cell induction by tiazofurin was shown to be synergistic with that produced by the antiviral agent ribavirin [4].
• Effects of tiazofurin on guanine nucleotide binding regulatory proteins in HL-60 cells [17].
• Moreover, incubation of HL-60 cells with guanosine or guanine (10(-6) to 10(-4) mol/L) prevents both the depletion of intracellular guanine ribonucleotides and the induction of myeloid maturation caused by the IMP dehydrogenase inhibitor, tiazofurin [21].
• When differentiation-linked cell surface marker expressions were determined in cells treated with trimidox and tiazofurin, a significantly increased fluorescence intensity was observed for the CD 11b (2.9-fold) [16].
• The effective dose for half-maximum induction by ribavirin was 3 times less than that for 50% inhibition of K562 proliferation; however, for tiazofurin and mycophenolic acid, it closely approximated the concentrations which suppressed cellular proliferation [22].

Gene context of Riboxamide

• This raised the possibility of calcium-dependent proteolysis due to the effects of tiazofurin, because in vitro GTP protects tTG against proteolysis by trypsin [23].
• To examine the effects of GTP on in situ TG activity, tiazofurin, a drug that selectively decreases GTP levels, was used [23].
• The tiazofurin resistance is mainly associated with the low NMNAT activity in the cell [24].
• Tiazofurin-induced autosecretion of IL-6 and hemoglobin production in K562 human leukemia cells [25].
• 8-Cl-cAMP and tiazofurin affect vascular endothelial growth factor production and glial fibrillary acidic protein expression in human glioblastoma cells [26].

Analytical, diagnostic and therapeutic context of Riboxamide

• Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by the synthetic "C" nucleoside analogs, tiazofurin and selenazofurin. A new strategy for cancer chemotherapy [9].
• Northern blot analysis of MEL cells treated with 7 mumol/L tiazofurin demonstrated accumulation of both alpha- and beta-globin RNA transcripts [3].
• Furthermore, tiazofurin treatment resulted in inhibition of N-formylmethionylleucylphenylalanine-induced stimulation of phospholipase C. Taken together, these results indicate that tiazofurin acts at least in part by inhibiting the ability of G proteins to function as transducers of intracellular signals [17].
• Tiazofurin levels were measured using a high-pressure liquid chromatography assay, and pharmacokinetic studies were performed in patients treated at each dose level [27].
• Extension of these approaches to the use of tiazofurin, for which biochemical markers and experimental combination chemotherapy leads are now available, would support the rational clinical development of tiazofurin combinations [28].

References