Pyrithiamine (hydrobromide)
(Synonyms: 抗硫胺氢溴酸) 目录号 : GC44790Pyrithiamine (hydrobromide)是一种硫胺素类似物，可抑制硫胺素（维生素B1）的代谢。
Cas No.:534-64-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
HeLa cells |
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Preparation method |
Cells were incubated for four days in 10μM Pyrithiamine (hydrobromide) in low thiamine medium prior to irradiation. |
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Reaction Conditions |
10μM; 4 days |
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Applications |
dATP, dCTP, dGTP and dTTP were all reduced in cells treated with Pyrithiamine (hydrobromide). |
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Animal experiment [2]: |
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Animal models |
AD model mice、WT mice |
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Preparation method |
mice were randomly divided into four groups respectively: control group, Pyrithiamine(hydrobromide) 250μg/kg/day group (hereafter the PT250 group), Pyrithiamine(hydrobromide) 500μg/kg/day group (PT500 group) and diet-induced TD group. The mice in TD group were fed a pelleted thiamine-depleted diet for four weeks. The control and PT groups received a normal thiamine-containing diet for 4 weeks. PT250 and PT500 groups received a daily intraperitoneal injection of Pyrithiamine(hydrobromide) (250 or 500μg/kg/day) for 4 weeks. |
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Dosage form |
250 or 500μg/kg/day; i.p. |
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Applications |
Pyrithiamine(hydrobromide) treatment significantly impairs the cognitive functions of wild-type mice, but has no corresponding effects on ADmodel mice that already have obvious cognitive impairment. |
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References: [1]Tiwana G S, Prevo R, Buffa F M, et al. Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen[J]. Oncotarget, 2015, 6(8): 5978. [2]Zhao J, Sun X, Yu Z, et al. Exposure to pyrithiamine increases β-amyloid accumulation, Tau hyperphosphorylation, and glycogen synthase kinase-3 activity in the brain[J]. Neurotoxicity research, 2011, 19: 575-583. |
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Pyrithiamine (hydrobromide) is a thiamine analogue that inhibits the metabolism of thiamine (vitamin B1)[1]. Pyrithiamine (hydrobromide) has high affinity to thiamine transporters in neurons, with a Kd of approximately 60 nM[2]. Pyrithiamine (hydrobromide) is also a substrate of thiamine pyrophosphate kinase (TPK) and can be converted into pyrithiamine pyrophosphate (PPP)[3]. Pyrithiamine (hydrobromide) can be used in microbial culture to inhibit the growth of microorganisms that require thiamine[4].
In vitro, Pyrithiamine (hydrobromide) (10μM) treated the HeLa cell line for 4 days, significantly reducing cellular nucleotide levels, and intracellular dATP, dCTP, dGTP and dTTP were all reduced[5]. Pyrithiamine (hydrobromide) (0.25mM) treated Neuro 2a cells, resulting in a strong reduction in intracellular ThDP levels, and the cells began to die after 48 hours [6].
In vivo, Pyrithiamine (hydrobromide) (250 or 500 μg/kg/day) treated mice by intraperitoneal injection for 4 weeks, causing thiamine deficiency, leading to cognitive dysfunction and neuropathological changes in wild-type mice, but it had no effect on existing mice. There is no corresponding effect on AD model mice with obvious cognitive impairment [7]. Pyrithiamine (hydrobromide) (0.5g/kg) was administered intraperitoneally to rats for 11 days, causing thiamine deficiency, leading to enlargement of the lateral ventricles and reduced levels of choline-containing compounds in the body [8].
References:
[1] Chauhan A, Srivastva N, Bubber P. Thiamine deficiency induced dietary disparity promotes oxidative stress and neurodegeneration[J]. Indian Journal of Clinical Biochemistry, 2018, 33: 422-428.
[2] Mulholland P J, Self R L, Stepanyan T D, et al. Thiamine deficiency in the pathogenesis of chronic ethanol-associated cerebellar damage in vitro[J]. Neuroscience, 2005, 135(4): 1129-1139.
[3] Liu J Y, Timm D E, Hurley T D. Pyrithiamine as a substrate for thiamine pyrophosphokinase[J]. Journal of biological chemistry, 2006, 281(10): 6601-6607.
[4]Brandenburger E, Gressler M, Leonhardt R, et al. A highly conserved basidiomycete peptide synthetase produces a trimeric hydroxamate siderophore[J]. Applied and Environmental Microbiology, 2017, 83(21): e01478-17.
[5]Tiwana G S, Prevo R, Buffa F M, et al. Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen[J]. Oncotarget, 2015, 6(8): 5978.
[6]Sambon M, Napp A, Demelenne A, et al. Thiamine and benfotiamine protect neuroblastoma cells against paraquat and β-amyloid toxicity by a coenzyme-independent mechanism[J]. Heliyon, 2019, 5(5).
[7]Zhao J, Sun X, Yu Z, et al. Exposure to pyrithiamine increases β-amyloid accumulation, Tau hyperphosphorylation, and glycogen synthase kinase-3 activity in the brain[J]. Neurotoxicity research, 2011, 19: 575-583.
[8]Zahr N M, Sullivan E V, Rohlfing T, et al. Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo[J]. Psychopharmacology, 2016, 233: 2675-2686.
Pyrithiamine (hydrobromide)是一种硫胺素类似物，可抑制硫胺素（维生素B1）的代谢[1]。Pyrithiamine (hydrobromide)与神经元中的硫胺素转运蛋白具有高亲和力，Kd约为60 nM[2]。Pyrithiamine (hydrobromide)也是硫胺素焦磷酸激酶（TPK）的底物，可以转化为吡啶硫胺焦磷酸盐（PPP）[3]。Pyrithiamine (hydrobromide)可用于微生物培养，抑制需要硫胺素的微生物生长[4]。
在体外，Pyrithiamine (hydrobromide)（10μM）处理HeLa细胞系4天，显著降低了细胞核苷酸水平，细胞内dATP、dCTP、dGTP和dTTP都被还原[5]。Pyrithiamine (hydrobromide)（0.25mM）处理Neuro 2a细胞，导致细胞内ThDP水平强烈降低，48h后细胞开始死亡[6]。
在体内，Pyrithiamine (hydrobromide)（250 or 500μg/kg/day）通过腹腔注射处理小鼠4周，引起硫胺素缺乏，导致野生型小鼠的认知功能障碍和神经病理变化，但对已有明显认知障碍的AD模型小鼠无相应影响[7]。Pyrithiamine (hydrobromide)（0.5g/kg）通过腹腔注射处理大鼠11天，引起硫胺素缺乏，导致侧脑室扩大，体内含胆碱化合物水平降低[8]。
| Cas No. | 534-64-5 | SDF | |
| 别名 | 抗硫胺氢溴酸 | ||
| 化学名 | 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-hydroxyethyl)-2-methyl-pyridinium, bromide, monohydrobromide | ||
| Canonical SMILES | CC1=[N+](CC2=C(N)N=C(C)N=C2)C=CC=C1CCO.[Br-].Br | ||
| 分子式 | C14H19N4O•HBr•Br | 分子量 | 420.1 |
| 溶解度 | 5mg/mL in PBS (pH 7.2) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3804 mL | 11.9019 mL | 23.8039 mL |
| 5 mM | 0.4761 mL | 2.3804 mL | 4.7608 mL |
| 10 mM | 0.238 mL | 1.1902 mL | 2.3804 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Model of Wernicke's encephalopathy
Arch Neurol 1981 Jun;38(6):350-4.PMID:7236062DOI:10.1001/archneur.1981.00510060052007.
After a week on a thiamine-free diet and daily injections of Pyrithiamine hydrobromide, a group of rats began to lose weight; soon thereafter hypothermia, piloerection, and ataxia developed, followed by convulsions and death. Neuropathologic examination disclosed hemorrhagic necrotic lesions in the thalamus, hypothalamus, collicular plate, vestibular nuclei, and inferior olives. The control groups did not show neurologic signs or neuropathologic abnormalities. The lesions in thiamine-deficient rats were similar in character and distribution to those of human Wernicke's disease. Because this experimental regimen produces neuropathologic changes rapidly and consistently, this animal model should be useful in studies designed to examine the pathophysiologic aspects of experimental Wernicke's disease in particular and CNS thiamine deficiency in general.
Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen
Oncotarget 2015 Mar 20;6(8):5978-89.PMID:25788274DOI:10.18632/oncotarget.3468.
Colony formation is the gold standard assay for determining reproductive cell death after radiation treatment, since effects on proliferation often do not reflect survival. We have developed a high-throughput radiosensitivity screening method based on clonogenicity and screened a siRNA library against kinases. Thiamine pyrophosphokinase-1 (TPK1), a key component of Vitamin B1/thiamine metabolism, was identified as a target for radiosensitization. TPK1 knockdown caused significant radiosensitization in cancer but not normal tissue cell lines. Other means of blocking this pathway, knockdown of thiamine transporter-1 (THTR1) or treatment with the thiamine analogue Pyrithiamine hydrobromide (PyrH) caused significant tumor specific radiosensitization. There was persistent DNA damage in cells irradiated after TPK1 and THTR1 knockdown or PyrH treatment. Thus this screen allowed the identification of thiamine metabolism as a novel radiosensitization target that affects DNA repair. Short-term modulation of thiamine metabolism could be a clinically exploitable strategy to achieve tumor specific radiosensitization.
In vivo localized proton NMR spectroscopy of thiamine-deficient rat brain
Magn Reson Med 1995 Sep;34(3):313-8.PMID:7500868DOI:10.1002/mrm.1910340306.
Thiamine deficiency (TD) in rats produces lesions similar to those found in humans suffering from Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 29) were deprived of thiamine via a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist Pyrithiamine hydrobromide. Spectra were obtained by using the STEAM sequence. No significant change occurred in the ratio of Cr/NAA, while the ratio of Cho/NAA declined significantly (60 +/- 11%) on Day 14. Eleven rats received intraperitoneal injections of thiamine hydrochloride at the end of 12 days, and dose-dependent recovery in Cho/NAA was observed.
In vivo and in vitro proton NMR spectroscopic studies of thiamine-deficient rat brains
J Magn Reson Imaging 2001 Feb;13(2):163-6.PMID:11169820DOI:10.1002/1522-2586(200102)13:2<163::aid-jmri1025>3.0.co;2-z.
Thiamine deficiency (TD) in rats produces lesions similar to those found in humans with Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 24) were deprived of thiamine in a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist Pyrithiamine hydrobromide for 12 days (0.5 mg/kg). In rats with TD, significant changes were observed in the choline peak (reduction and dose-dependent recovery after thiamine replenishment), which was confirmed by the extraction study. Changes were mainly due to the reduction in glycerophosphorylcholine (GPC), suggesting that a reduction in GPC may be relevant to the primary biochemical lesion in TD. These data are compatible with the hypothesis that a decrease in choline compounds is the cause of the biochemical abnormalities that precede neuroanatomic damage characteristic of Wernicke's encephalopathy.
The effects of single and repeated episodes of thiamin deficiency on memory in alcohol-consuming rats
Alcohol 1997 Jan-Feb;14(1):81-91.PMID:9014028DOI:10.1016/s0741-8329(96)00111-5.
The underlying pathogenesis of Korsakoff's syndrome, an amnesic disorder most commonly found in alcoholics, is not well understood. Chronic alcoholism is associated with thiamin deficiency and current thinking is that this may be the causal factor. In Experiment 1, rats were given a 20% (v/v) ethanol/water mix as their only source of fluid for 156 days. Three groups were made thiamin deficient through the combination of a thiamin-deficient diet and the centrally acting thiamin antagonist pyrithiamin hydrobromide, after 4, 15, and 26 weeks exposure to ethanol, respectively. The control group was given ad lib access to laboratory chow and water throughout this period. There were no differences between groups on either the working or reference versions of the Morris water tank paradigm. In Experiment 2, to test the hypothesis that a single bout of thiamin deficiency, with or without concurrent alcohol intake, is not sufficient to cause severe memory impairments, two groups of rats were subjected to three bouts of thiamin deficiency. One of these groups consumed an ethanol/water mix, the other tap water. A third group was made thiamin deficient on only one occasion. The control group was not made thiamin deficient and consumed lab chow and tap water throughout. Once again, there were no between-group differences in the data derived from testing in either the eight-arm radial maze or the Morris water tank task. These experiments indicate that the aetiology of Korsakoff's syndrome is more complex than previously thought.