TY - JOUR. T1 - Combined preconditioning and in vivo chemoselection with 6-thioguanine alone achieves highly efficient reconstitution of normal hematopoiesis with HPRT-deficient bone marrow. AU - Hacke, Katrin. AU - Szakmary, Akos. AU - Cuddihy, Andrew R.. AU - Rozengurt, Nora. AU - Lemp, Nathan A.. AU - Aubrecht, Jiri. AU - Lawson, Gregory W.. AU - Rao, Nagesh P.. AU - Crooks, Gay M.. AU - Schiestl, Robert H.. AU - Kasahara, Noriyuki. PY - 2012/1. Y1 - 2012/1. N2 - Purine analogs such as 6-thioguanine (6TG) cause myelotoxicity upon conversion into nucleotides by hypoxanthine-guanine phosphoribosyltransferase (HPRT). Here we have developed a novel and highly efficient strategy employing 6TG as a single agent for both conditioning and in vivo chemoselection of HPRT-deficient hematopoietic stem cells. The dose-response and time course of 6TG myelotoxicity were first compared in HPRT wild-type mice and HPRT-deficient transgenic mice. Dosage and schedule parameters were optimized to employ 6TG for ...
6-Thioguanine-resistant mutants were induced in V79 Chinese hamster cells with 2-aminopurine, ICR-170 and hycanthone. Samples of mutants of different origin were treated with EMS or 1CR-170 and plated in HAT medium for selection of revertants. In the result, a significant fraction of HAT-resistant clones was not 6-thioguanine-sensitive as would have been expected from a genuine reversion to wild type.
Clinical studies have shown that the absorption of an oral dose of thioguanine in humans is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%). Following oral administration of 35S-6-thioguanine, total plasma radioactivity reached a maximum at 8 hours and declined slowly thereafter. Parent drug represented only a very small fraction of the total plasma radioactivity at any time, being virtually undetectable throughout the period of measurements.. The oral administration of radiolabeled thioguanine revealed only trace quantities of parent drug in the urine. However, a methylated metabolite, 2-amino-6-methylthiopurine (MTG), appeared very early, rose to a maximum 6 to 8 hours after drug administration, and was still being excreted after 12 to 22 hours. Radiolabeled sulfate appeared somewhat later than MTG but was the principal metabolite after 8 hours. Thiouric acid and some unidentified products were found in the urine in small amounts. Intravenous ...
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Effects of 6-thioguanine on PTHrP content in the media of cultured MDA-MB-231 cells plated onto 48-well plates and grown to near confluence. Cells were washed and treated with serum-free media containing 6-thioguanine in the indicated concentrations for 48 hours. PTHrP concentrations in conditioned media were corrected for cell number. The detection limit of the assay is ∼0.5 pM/L ...
Definition of tioguanine in the Definitions.net dictionary. Meaning of tioguanine. What does tioguanine mean? Information and translations of tioguanine in the most comprehensive dictionary definitions resource on the web.
Chinese hamster ovary cells synchronized by mitotic detachment were treated with 5-fluorodeoxyuridine (FdUrd), 0.2 µg/ml, at various times in the cell cycle. FdUrd treatment in the early S period induced resistance to 6-thioguanine. Treatment of asynchronous cells with FdUrd caused little increase in 6-thioguanine resistance over the spontaneous frequency. Mitotic selection thus enhances the probability of a cell being in the portion of S period receptive to mutation. These observations suggest that FdUrd treatment leads to mutagenesis at the growing points of DNA replication.. ...
ECCO - European Crohn´s and Colitis Organisation. The European Crohn\s and Colitis Organisation is a highly active non-profit association focusing on Inflammatory Bowel Diseases (IBD).
I will begin with the positive. Today we started the last phase before maintenance, Delayed Intensification. Today was a little like the beginning of the end. This phase totals 57 days (if everything goes as planned). We are looking to be in maintenance towards the end of January. After January Camis hair should start to grow back and we will only have to go to clinic for chemo once a month...this is HUGE and we are getting so close I can taste it! This is all great and exciting, the only drawback is we have to make it through this BRUTAL round before we get there. Cami will be on 9 different drugs in this round; Dexamethasone (steroids again...blahhh), Vincristine, Doxorubicin, PEG-asparaginase, Thioguanine, Cytarabine, Intrathecal Methorexate, and Septra ...
The thiopurine drugs are purine antimetabolites that are useful in the treatment of acute lymphoblastic leukemia, autoimmune disorders (e.g., Crohn disease, rheumatoid arthritis), and organ transplant recipients. The thiopurine drugs, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), and azathioprine (AZA) are prodrugs that require intracellular activation to 6-thioguanine nucleotides (6-TGN). This activation is catalyzed by multiple enzymes. The cytotoxic effects of thiopurine drugs are achieved mainly through incorporation of 6-TGN into DNA and RNA. The pathway that leads to synthesis of active cytotoxic 6-TGN is in competition with inactivation pathways catalyzed by thiopurine methyltransferase (TPMT). Evaluation of this pathway is important because the level of 6-TGN measured in red blood cells have been correlated with both thiopurine therapeutic efficacy and toxicity such as myelosuppression.. TPMT activity is inherited as a monogenic codominant trait, and variable TPMT activity is associated ...
Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. ...
Le page, G and White, S, "Scheduling of arabinosylcytosine (ara-c) and 6-thioguanine (6-tg) therapy. Abstr." (1972). Subject Strain Bibliography 1972. 390 ...
The best-studied example of genetic variation within a DME and its effect on toxicity is the interaction between variants in thiopurine methyltransferase (TPMT) and toxicity with the thiopurine antimetabolites 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). 6-MP is used as an immunosuppressant for some nonmalignant conditions, such as inflammatory bowel diseases (12, 13), and is one of the backbones of treatment in the most frequent pediatric malignancy, acute lymphoblastic leukemia [ALL (14)]. The thiopurines are prodrugs that are converted by multiple enzymes into thioguanine nucleotides (TGN), which are then incorporated into DNA. Inactivation of TGN occurs by 2 main mechanisms: oxidation by xanthine oxidase and methylation by TPMT. Xanthine oxidase activity is negligible in hematopoietic tissues, so these cells rely on TPMT for TGN inactivation (15).. Struck by the wide interpatient variability in both response and toxicity observed in patients treated with 6-MP, Weinshilboum and Sladek ...
The test item was tested in the standard plate incorporation test in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 at concentrations from 0.16 to 100 µg/plate both in the presence and absence of metabolic activation. No cytotoxicity was observed at any concentration. At concentrations of 20 µg/plate and above, precipitation of the test stubstance was observed. An increase in the number of revertant colonies could not be observed up to the highest dose of 100 µg/plate. Vat Blue 20 is thus not mutagenic in the Ames test under the experimental conditions chosen. The structural analogue was examined for mutagenic activity by assaying for the induction of 6-thioguanine resistant mutants in Chinese hamster V79 cells after in vitro treatment. Experiments were performed both in the absence and presence of metabolic activation, using liver S9 fraction from rats pre-treated with phenobarbitone and betanaphthoflavone. Test item suspensions/solutions were prepared using ...
Do not use mercaptopurine if you are pregnant. It could harm the unborn baby. You should not use mercaptopurine if you are allergic to it, or if you have ever used mercaptopurine or thioguanine (Tabloid) and they were not effective in treating your condition. Some people using mercaptopurine have developed a rare fast-growing type of lymphoma (cancer). This condition affects the liver, spleen, and bone marrow, and it can be fatal. This has occurred mainly in teenagers and young adults using mercaptopurine or similar medicines to treat Crohns disease or ulcerative colitis. Call your doctor at once if you have any of the following symptoms: fever, night sweats, itching, loss of appetite, weight loss, tiredness, feeling full after eating only a small amount, pain in your upper stomach that may spread to your shoulder, nausea, easy bruising or bleeding, pale skin, feeling light-headed or short of breath, rapid heart rate, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). ...
Hybrid generated by fusion of 6-thioguanine-resistant mutant of mouse neuroblastoma N4TG3 and 8-bromodeoxyuridine-resistant mutant of mouse L cell fibroblast line B82 using inactivated Sendai virus. The fusion of N4TG3 x B82 generated two types of hybrid cells: neuronal resembling the neuroblastoma and epithelioid with clearly visible nucleus. 328/8 is of the neuronal type ...
BACKGROUND:: The value of azathioprine metabolites (6-thioguanine nucleotides [6-TGN]) in monitoring clinical treatment response is still controversially discussed. Data regarding thiopurine metabolite levels and endoscopic improvement are lacking. METHODS:: Data were analyzed post hoc from a 1-year, multicenter, double-blind, double-dummy, randomized trial comparing azathioprine 2.0 to 2.5 mg/kg per day ...
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... is used to treat acute lymphoblastic or lymphocytic leukemia. Mercaptopurine is sometimes given with other cancer medications. Mercaptopurine may also be used for purposes not listed in this medication guide.
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An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. [PubChem]
6-mercaptopurine is given by mouth and intravenously (IV) to treat cancer. Find 6-mercaptopurine side effects, allergic reactions, and more.
6-mercaptopurine monohydrate testing. Laboratory testing for CAS number 6112-76-1. . This chemical is light yellow crystalline powder
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The three thiopurine drugs azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used to treat several diseases, including inflammatory bowel disease (IBD). They are pro-drugs and are believed to act through the formation of thioguanine nucleotides (TGNs). Other important metabolites are the methylthioinosine nucleotides (meTINs). These metabolites are active in the white blood cells (WBCs).Most patients respond well to the thiopurine drugs but up to a third have to modify or discontinue their treatment due to adverse events or a lack of therapeutic effects. This could be caused by inter-patient variability in the metabolism of the drugs. Therapeutic drug monitoring (TDM) of thiopurine nucleotides in red blood cells (RBCs) is used to guide treatment. Current routine assays measure the nucleotides after hydrolysation to nucleic bases and are therefore unable to distinguish between mono-, di-, and triphosphates. Recently it was shown that these assays failed to predict the ...
Structure-activity ATPase studies with other substituted purines. To obtain information concerning the mechanism of action of NSC35866, we next did structure-activity ATPase studies, including 12 other substituted purine analogues of different chemical classes ( Fig. 1). Two C9-substituted purine analogues, 9-benzylguanine and acyclovir (the latter being an inhibitor of viral DNA polymerase ref. 37), had no inhibitory effect on the ATPase reaction of human topoisomerase IIα at concentrations up to 300 μmol/L (data not shown). 6-Chloroguanine had also no inhibitory effect on the topoisomerase II ATPase reaction (data not shown).. Because NSC35866 is a S6-substituted thioether of guanine, we also assessed the ability of two other S6-substituted thioether purine analogues, 6-methylthioguanine and azathioprine (the latter being used as an antimetabolite prodrug in the clinic; ref. 38), to inhibit the topoisomerase II ATPase reaction ( Fig. 3B). Both compounds were capable of inhibiting ...
Angiogene Pharmaceuticals was developing bioreductive prodrugs of 6-mercaptopurine (6-MP) or 6-thioguanine (6-TG) for the treatment of cancer. Tissue hypoxia is
This review analyzes which people have lack of strength or dynamic energy with Stavudine. preparation to be used patients with care children are considered the treatment of choice for enteric stomach pain (severe) in spontaneous pregnancy. Combination is of Thioguanine and dangerous substance exerts an additive relaxant effect on physical human detrusor and prostatic tissues in vitro.. ...
Berenbaum, M C., "Role of mitosis and mitotic inhibition in the immuno-suppressive action of thioguanine." (1966). Subject Strain Bibliography 1966. 439 ...
Measurement of TPMT activity is encouraged prior to commencing the treatment of patients with thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine. Patients with low activity (10% prevalence) or especially absent activity (prevalence 0.3%) are at a heightened risk of drug-induced bone marrow toxicity due to accumulation of the unmetabolised drug. Reuther et al. found that about 5% of all thiopurine therapies will fail due to toxicity. This intolerant group could be anticipated by routine measurement of TPMT activity. There appears to be a great deal of variation in TPMT mutation, with ethnic differences in mutation types accounting for variable responses to 6MP.[9][12] Genetic variants of TPMT have also been associated with cisplatin-induced ototoxicity in children.[13] TPMT is now listed as a pharmacogenomic biomarker for adverse drug reactions to cisplatin by the FDA.[14] ...
The goal of this clinical research study is to learn if the combination of 6-Thioguanine, Xeloda (capecitabine), and Celebrex (celecoxib) with Temodar (temozolomide) or Lomustine (CCNU) is effective in the treatment of recurrent or progressive anaplastic glioma or glioblastoma multiforme in patients who have failed previous treatments. The safety of these combination treatment will also be studied.. Objectives:. 1.1 To determine the efficacy, as measured by 12 month progression-free survival, of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in the treatment of patients with recurrent and/or progressive anaplastic gliomas or glioblastoma multiforme.. 1.2 To determine the long-term toxicity of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in recurrent anaplastic glioma or glioblastoma multiforme patients treated in this manner.. 1.3 To determine the clinical relevance of genetic subtyping tumors as a predictor of response to this ...
Approximately 0.3% of the population has a profound genetic deficiency of thiopurine methyltransferase, the major route for detoxification of thiopurines used in immunosuppression and oncology.. These patients develop severe marrow suppression if given usual doses of a thiopurine drug or prodrug. The condition is inherited as an autosomal recessive trait, and about 11% of the population are carriers.. Carriers may also show decreased tolerance to the drugs, although not as severely as the severely deficient patients.. ...
Thiopurine methyltransferase (TPMT) testing is important in the detection of individuals with altered TPMT activity who are at risk for severe hematopoietic toxicity when taking thiopurine medications (6-mercaptopurine, azathioprine, and 6-thioguanine). This webinar will outline the different tests to detect patients who are at risk for thiopurine-related toxicity and the advantages of each test. It is intended to educate clinicians and increase their confidence when treating patients with thiopurine medications.. ...
Azathioprine and 6-mercaptopurine (AZA/6MP) are effective immunosuppressives commonly used for the treatment of inflammatory bowel disease (IBD). The mercaptopurine metabolites, 6-thioguanine (6TG) and 6-methylmercaptopurine ...
Thiopurine methyl transferase (TPMT) is an enzyme catalysing the methylation of 6-MP, competing with xanthine oxidase (XO) and hypoxanthine guanine phosphoribosyl transferase (HGPRT) to determine the amount of 6-MP metabolised to cytotoxic thioguanine nucleotides. Allelic polymorphisms in the TPMT gene predict the activity of the enzyme such that 1 in 10 of the population are heterozygous and have approximately 50% of normal activity, whilst 1 in 300 are completely deficient. As a result, these individuals are at high risk of severe myelosuppression. Conversely, individuals with very high levels of TPMT activity are hyper-methylators in whom clinical response is less likely. Prior knowledge of TPMT status avoids exposure of individuals with zero TPMT to potentially fatal treatment with AZA or 6-MP and provides one of the best examples of predictive pharmacogenetics in therapeutics. This article reviews literature on the role of TPMT measurement prior to treatment with thiopurines and provides ...
... is an enzyme that breaks down a class of drugs called thiopurines. TPMT tests are used to identify people at risk of developing severe side effects from thiopurine treatment.
PRIMARY OBJECTIVES:. I. Determine the impact of interventions proposed in intervention program (IP) versus (vs.) education alone (EDU) on adherence to oral 6MP (mercaptopurine) in children with acute lymphoblastic leukemia (ALL). Adherence will be measured by: i) Medication Event Monitoring Systems (MEMS) (primary measure of adherence to oral 6MP, providing real-time data; ii) red cell thioguanine nucleotide (TGN) levels (providing data on chronic, systemic 6MP exposure).. SECONDARY OBJECTIVES:. I. Examine the modifying effect of sociodemographic and psychosocial variables, and the mediating effect of health beliefs/ knowledge on change in adherence with intervention.. II. Determine impact of IP vs. EDU on risk of relapse of ALL.. OUTLINE: Patients are randomized to 1 of 2 intervention arms.. ARM I: Patients receive the Patients Supply Kit containing an electronic pill monitoring system, a MEMS? medication bottle with TrackCap? with standard resistant cap, and written instructions for the ...
BACKGROUND: The activity of the human enzyme thiopurine methyltransferase (TPMT) varies greatly between individuals because of genetic polymorphism. TPMT is involved in the detoxification and activation of thiopurines such as 6-mercaptopurine, 6-thioguanine, and azathioprine. These drugs are used in the treatment of acute lymphoblastic leukemia and inflammatory bowel disease. A total of 29 sequence variants have been identified so far in the TPMT gene. However, most of these variants are rare and not fully characterized. METHODS AND RESULTS: In this study, we describe the identification and characterization of a novel TPMT sequence variant, originally found in a Swedish man of Italian origin. Sequencing of the variable number tandem repeats region of the TPMT promoter and exons III-X revealed a T-to-C transition at nucleotide 611, causing an amino acid substitution from isoleucine to threonine at amino acid 204, positioned in an α-helix, approximately 16 Å from the active site. This new ...
Introduction Measuring azathioprine or mercaptopurine (AZA) metabolite levels 6-TGN and 6-MMPN allows identification of patients who are: 1. Non compliant with their medication, 2. On a sub-optimal doe, 3. On a supra-therapeutic dose, 4. Are preferentially metabolising azathioprine to methylated metabolites (6-MMPN:6-TGN ratio , 11).. Our own and others published data demonstrate that measuring metabolite levels in patients failing azathioprine therapy followed by appropriate changes in dosing and/or the addition of allopurinol (with 75% dose reduction in AZA) can result in clinical remission in the majority of patients 1. We report the outcome of the routine measurement of metabolite levels in patients treated with AZA who were in a clinical remission without side effects or abnormal liver function tests (LFTs).. ...
Result 64 individuals studied, median age 14 years. Underlying diagnoses were "IBD" (54/64) and "other" (10/64). 59 treated with AZA, 5 with 6-MP. 95 separate measurements were made. TPMT phenotype was measured in 51/64 patients,40/51 had "normal" phenotype, and 11/51 had heterozygous TPMT mutations. Initial 6-TGN levels were higher in heterozygotes (median levels 836 vs 328, p=0.001) at comparable doses of thiopurine (median 1.9 vs 2.2 mg/kg, p=0.11). On first measurement, only 30% patients had 6-TGN levels within therapeutic levels. 30% were subtherapeutic and 40% were supra-therapeutic. 9% had 6-TGN levels ,800. Toxicity occurred in 8 cases (9%). Leucopaenia (WBC,4) had a sensitivity of 12.5% in predicting supra-therapeutic 6-TGN levels. Concomitant use of 5-ASA did not significantly affect 6-TGN levels at comparable doses (median (6-TGN) "5-ASA" 393 vs 451 "no 5-ASA", p=0.26). In total, management was changed in 39 cases (41%). 6 cases of total non-compliance were exposed. 33/39 of these ...
Functional genomic screening is largely used for identifying the essential genes for a specific cellular process. RNA interference (RNAi) [51] has been dominantly applied for genome-wide screening; however, the off-target effects of RNAi has limited its applications [52-54]. In addition, RNAi could not be used for silencing RNAs located in nucleus. The CRISPR-Cas9 system has been successfully used in various genome-scale loss of function screening [55-58]. Using a genome-scale lentiviral sgRNA library, all expected genes of the DNA mismatch repair pathway have been identified in screening for resistance to the nucleotide analog 6-thioguanine, and numerous genes corresponding to fundamental processes have been obtained with a negative selection screening for essential genes [55]. A genome-scale CRISPR-Cas9 knockout (GeCKO) library has been developed and successfully used for screening genes essential for cell viability in cancer and pluripotent stem cells and for genes associated with the ...
1. Berenbeim, J.A., Owens, S., Schmidt Patterson, C.M., de Vries, M.S., "Molecular Mechanisms of the Photostability of Common Madder Chromophores Alizarin and Purpurin and Hydroxy-Substituted Anthraquinones" Manuscript in Preparation. 2. Berenbeim, J.A., Siouri, F., Boldissar, S., Gate, G., Haggmark, M., Aboulache, B., Cohen, T., de Vries, M.S.,"Excited State Dynamics of Isocytosine; a Hybrid Case of Canonical Nucleobase Photodynamics" Manuscript Submitted. 3. Siouri, F., Boldissar, S., Berenbeim, J.A., de Vries, M.S., "Excited State Dynamics of 6-Thioguanine" J. Phys. Chem. 2017.. 4. Owens, S., Berenbeim, J.A., Ligare, M., Gulian, L., Siouri, F., Boldissar, S., Tyson-Smith, S., Wilson, G., Ford, A.,De Vries, M.S., "Direct Analysis of Xanthine Stimulants in Archaeological Vessels by laser desorption REMPI" Anal. Chem. 2017.. 5. Owens, S. C., Berenbeim, J. A., Patterson, C. S., Dillon, E. P., de Vries, M.S., "Sub-Micron Proximal Probe Thermal Desorption and Laser Mass Spectrometry on Painting ...
In this article, we have presented evidence for the cellular uptake and GSH-mediated metabolism of the structurally novel prodrugs AVTG and AVTP to their parent thiopurines 6-TG and 6-MP, respectively. Furthermore, our results demonstrate that intracellular concentrations of 6-TG were higher after incubations with AVTG compared with cells incubated with 6-TG. Moreover, although the prodrugs exhibited cytotoxicity that was similar to or exceeded that of the parent thiopurines, the in vivo administration of the prodrugs did not lead to bone marrow toxicity as was observed after 6-TG administration.. Structurally, AVTG and AVTP are α, β-unsaturated conjugates of 6-TG and 6-MP, respectively. The α, β-unsaturated moiety allows the prodrugs to react with cellular nucleophiles to yield the parent thiopurine and a nucleophile-butenone conjugate. Our results show that this bioactivation is selectively mediated by sulfhydryl nucleophiles such as GSH. A similar mechanism of bioactivation has been ...
Purixan (mercaptopurine) is used to treat acute lymphoblastic leukemia. Includes Purixan side effects, interactions and indications.
This study examined thiopurine methyltransferase (TPMT) and the relationship to thioguanine nucleotides (TGN) and methylthioinosine monophosphate (meTIMP) in a large Swedish patient population. The current hypothesis is that the cytotoxic effects of thiopurine drugs are mediated by the incorporation of TGN into DNA. The authors assayed the TPMT activity in red blood cells from 1151 subjects and the concentrations of TGN (n = 602) and meTIMP (n = 593) from patients treated with thiopurine drugs. The TPMT frequency distribution in both adults and children showed some differences from what had been found in unselected general populations. Children had lower median TPMT activity than adults (12.0 versus 12.9 U/mL RBC, P < 0.001). Relative differences in both TGN formation [medians: normal TPMT, 1.3, intermediate TPMT, 3.3, low TPMT, 47.9 pmol/8 × 108 RBC per mg azathioprine (AZA), P < 0.001] and meTIMP formation (medians: normal TPMT, 13, intermediate TPMT, 7.3, low TPMT, 0 pmol/8 × 108 RBC per mg ...
Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds including thiopurine drugs such as 6-mercaptopurine, 6-thioguanine and azathioprine. TPMT activity exhibits genetic variation and show
Azathioprine is well absorbed following oral administration. Maximum serum radioactivity occurs at 1 to 2 hours after oral 35S-azathioprine and decays with a half-life of 5 hours. This is not an estimate of the half-life of azathioprine itself, but is the decay rate for all 35S-containing metabolites of the drug. Because of extensive metabolism, only a fraction of the radioactivity is present as azathioprine. Usual doses produce blood levels of azathioprine, and of mercaptopurine derived from it, which are low (,1 mcg/mL). Blood levels are of little predictive value for therapy since the magnitude and duration of clinical effects correlate with thiopurine nucleotide levels in tissues rather than with plasma drug levels. Azathioprine and mercaptopurine are moderately bound to serum proteins (30%) and are partially dialyzable. (See OVERDOSAGE).. Azathioprine is metabolized to 6-mercaptopurine (6-MP). Both compounds are rapidly eliminated from blood and are oxidized or methylated in erythrocytes ...
In high school, the usual advice on multiple choice questions was to avoid picking always and never on multiple choice questions. A recent commentary (KH de Boer et al.Thiopurine Therapy in Inflammatory Bowel Diseases: Making New Friends Should Not Mean Losing Old OnesGastroenterol 2019; 156: 11-4) makes the point that never is probably the wrong…
Last year we saw many developmental activities through geneOmbios R&D effort that are now getting translated into active business through new cases being prescribed for testing in pharmacogenomics domain. We have recently come up analysis of a different gene in TPMT therapy that is found to contribute in toxicity due to treatment with thiopurine drugs. The gene named NUDT15 is found to have a nonsynonymous SNP in encoding p.Arg139Cys that is strongly associated with thiopurine-induced early leukopenia. Moreover the frequency of this mutation is higher in Asian population. Hence while assessing therapeutic dosage and toxicity due to TPMT treatment, it has become a necessity to perform genetic test to identify whether this mutation is present in an individual along with his status with TPMT alleles.. Acute lymphoblastic leukemia (ALL) is a cancer that affects the white blood cells. These cells fight infection and help protect the body against disease. Patients with ALL have too many immature ...
Antimetabolite A substance bearing a close structural resemblance to one required for normal physiological functioning, and exerting its effect by interfering with the utilization of the essential metabolite. It competes with, replaces, or antagonizes a particular metabolite; for example, ethionine is an antimetabolite of methionine.methotrexatefolic acidcancerCancercancercancer