2,3,4,5,6-pentahydroxy-hexanal | 15572-79-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3,4,5,6-pentahydroxy-hexanal
• 英文别名: glucose；galactose；mannose；hexose；D-glucose；2,3,4,5,6-Pentahydroxyhexanal
• CAS: 15572-79-9；8027-56-3；50-99-7；1990-29-0；5934-56-5；2595-97-3；25191-16-6；110187-42-3；45009-62-9；93780-23-5；3458-28-4；2595-98-4；4205-23-6
• 化学式: C₆H₁₂O₆
• 分子量: 180.158
• InChiKey: GZCGUPFRVQAUEE-UHFFFAOYSA-N

物化性质

• 熔点：
  150-152 °C(lit.)
• 溶解度：
  可溶于甲醇（轻微、加热、超声处理）、水（少量、超声处理）
• 物理描述：
  Watery odorless colorless liquid. Denser than water and soluble in water. Hence sinks in and mixes with water. (USCG, 1999)
• 颜色/状态：
  Colorless crystals or white granular powder
• 气味：
  Odorless
• 味道：
  Sweet
• 沸点：
  greater than 212 °F at 760 mm Hg (USCG, 1999)
• 密度：
  Density: 1.5620 at 18 °C/4 °C /alpha-Glucose/; 1.54 at 25 °C/4 °C /alpha-Glucose, monohydrate/; 1.5620 at 18 °C/4 °C; needles from alc ohol/beta-Glucose/
• 蒸汽压力：
  8.0X10-14 mm Hg at 25 °C /extrapolated from a higher solid-phase temperature range/
• 亨利常数：
  Henry's Law constant = 3.5X10-20 atm-cum/mol at 25 °C (est)
• 稳定性/保质期：

  在常温常压下保持稳定，应避免与强氧化剂接触。

• 旋光度：
  SPECIFIC OPTICAL ROTATION: +52.7 (WATER) @ 20 °C/D; MAX ABSORPTION (WATER): 282 NM (LOG E= 1.2); SADTLER REFERENCE NUMBER: 5455 (IR, PRISM); 199 (IR, GRATING)
• 自燃温度：
  Not flammable (USCG, 1999)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 解离常数：
  pKa = 12.92 at 0 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  6

ADMET

代谢

大肠杆菌在分批培养中以葡萄糖为食时，会伴随乙酸的外排，当葡萄糖耗尽时，细胞会消耗这些乙酸。这种葡萄糖-乙酸转换通常被描述为二阶段生长（两个连续的生长阶段）。在这里，我们通过分析生长参数和基因表达来研究细胞在葡萄糖耗尽后的生理和代谢特性。我们发现，在分批培养中以葡萄糖为食的大肠杆菌细胞在葡萄糖耗尽后会产生并消耗乙酸，但不会在乙酸上生长。乙酸被分解代谢，但关键的合成基因——如编码糖酵解途径中酶的基因——并未上调，因此阻止了生长。只有经过长时间接触低浓度乙酸，才观察到后述合成基因的诱导和生长，而高浓度乙酸可以加速这一过程。我们推测，这种乙酸分解代谢与乙酸合成代谢之间的脱钩可能是大肠杆菌在肠道不断变化环境中生存的优势。葡萄糖-乙酸转换是全面研究代谢适应性的宝贵实验模型，也是系统微生物学中开发建模方法的当前范例。然而，我们论文中报告的工作表明，大肠杆菌在葡萄糖-乙酸转换期间的代谢行为比迄今为止报道的要复杂得多。在葡萄糖耗尽后观察到了乙酸分解代谢与乙酸合成代谢之间的脱钩，这一现象之前并未报道。这一现象可能代表了大肠杆菌在肠道定植和持续存在期间优化碳资源利用的策略，对生物技术应用也具有重大意义。

Growth of Escherichia coli on glucose in batch culture is accompanied by the excretion of acetate, which is consumed by the cells when glucose is exhausted. This glucose-acetate transition is classically described as a diauxie (two successive growth stages). Here, we investigated the physiological and metabolic properties of cells after glucose exhaustion through the analysis of growth parameters and gene expression. We found that E. coli cells grown on glucose in batch culture produce acetate and consume it after glucose exhaustion but do not grow on acetate. Acetate is catabolized, but key anabolic genes--such as the genes encoding enzymes of the glyoxylate shunt--are not upregulated, hence preventing growth. Both the induction of the latter anabolic genes and growth were observed only after prolonged exposure to low concentrations of acetate and could be accelerated by high acetate concentrations. We postulate that such decoupling between acetate catabolism and acetate anabolism might be an advantage for the survival of E. coli in the ever-changing environment of the intestine. The glucose-acetate transition is a valuable experimental model for comprehensive investigations of metabolic adaptation and a current paradigm for developing modeling approaches in systems microbiology. Yet, the work reported in our paper demonstrates that the metabolic behavior of Escherichia coli during the glucose-acetate transition is much more complex than what has been reported so far. A decoupling between acetate catabolism and acetate anabolism was observed after glucose exhaustion, which has not been reported previously. This phenomenon could represent a strategy for optimal utilization of carbon resources during colonization and persistence of E. coli in the gut and is also of significant interest for biotechnological applications.

来源:Hazardous Substances Data Bank (HSDB)

代谢

当霍乱弧菌遇到营养压力时，它会激活（p）ppGpp介导的严格反应。relA和relV基因参与（p）ppGpp的产生，而spoT基因编码一种水解它的酶。在此，我们展示了细菌产生（p）ppGpp的能力在葡萄糖代谢中起着至关重要的作用。霍乱弧菌的（p）ppGpp产生缺陷型突变体（即deltarelAdeltarelV和deltarelAdeltarelVdeltaspoT突变体）在额外葡萄糖存在下由于无法控制的有机酸产生而失去了生存能力。相比之下，deltarelAdeltaspoT突变体，一种（p）ppGpp过度产生菌株，在相同葡萄糖浓度下表现出更好的生长。RNA测序分析显示，在第七次大流行O1菌株N16961中，由乙偶姻生物合成操纵子组成的基因转录显著升高，但在其（p）ppGpp(0)突变体中在葡萄糖刺激生长期间并未升高。在乙偶姻生物合成基因簇中的转座子插入导致deltarelAdeltaspoT突变体在葡萄糖诱导下失去生存能力，这进一步表明乙偶姻产生在葡萄糖丰富环境下的平衡生长中起着关键作用。额外删除编码乙偶姻产生负调控因子aphA的基因未能挽救（p）ppGpp(0)突变体免于葡萄糖介导的生长缺陷，表明（p）ppGpp介导的乙偶姻产生独立于AphA的存在。总的来说，我们的结果揭示，（p）ppGpp除了其作为严格反应介导者的已知角色外，还正向调控乙偶姻的产生，这有助于在葡萄糖丰富的环境中成功进行葡萄糖代谢，从而促进霍乱弧菌细胞的增殖，这种情况可能模拟人类肠道。

When V. cholerae encounters nutritional stress, it activates (p)ppGpp-mediated stringent response. The genes relA and relV are involved in the production of (p)ppGpp, whereas the spoT gene encodes an enzyme that hydrolyzes it. Herein, we show that the bacterial capability to produce (p)ppGpp plays an essential role in glucose metabolism. The V. cholerae mutants defective in (p)ppGpp production (i.e. deltarelAdeltarelV and deltarelAdeltarelVdeltaspoT mutants) lost their viability because of uncontrolled production of organic acids, when grown with extra glucose. In contrast, the deltarelAdeltaspoT mutant, a (p)ppGpp overproducer strain, exhibited better growth in the presence of the same glucose concentration. An RNA sequencing analysis demonstrated that transcriptions of genes consisting of an operon for acetoin biosynthesis were markedly elevated in N16961, a seventh pandemic O1 strain, but not in its (p)ppGpp(0) mutant during glucose-stimulated growth. Transposon insertion in acetoin biosynthesis gene cluster resulted in glucose-induced loss of viability of the deltarelAdeltaspoT mutant, further suggesting the crucial role of acetoin production in balanced growth under glucose-rich environments. Additional deletion of the aphA gene, encoding a negative regulator for acetoin production, failed to rescue the (p)ppGpp(0) mutant from the defective glucose-mediated growth, suggesting that (p)ppGpp-mediated acetoin production occurs independent of the presence of AphA. Overall, our results reveal that (p)ppGpp, in addition to its well known role as a stringent response mediator, positively regulates acetoin production that contributes to the successful glucose metabolism and consequently the proliferation of V. cholerae cells under a glucose-rich environment, a condition that may mimic the human intestine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

同一肿瘤类型内的异质性已被描述为复杂并在多个层面上发生。关于肿瘤集合内代谢水平的异质性，人们知之甚少，然而代谢途径与肿瘤中的生存信号高度相关。在这项研究中，我们分析了几种非小细胞肺癌（NSCLC）细胞系的葡萄糖代谢，并能够显示，NSCLC表现出独特的糖酵解代谢。遗传和药理干扰糖酵解对糖酵解速率高的NSCLCs具有选择性毒性。此外，高表达的己糖激酶-2，定位于线粒体，是依赖葡萄糖分解的NSCLCs的特征。我们的研究为NSCLCs的定量代谢多样性提供了证据，并表明葡萄糖代谢为NSCLCs提供了不同的生存益处。

Heterogeneity within the same tumor type has been described to be complex and occur at multiple levels. Less is known about the heterogeneity at the level of metabolism, within a tumor set, yet metabolic pathways are highly relevant to survival signaling in tumors. In this study, we profiled the glucose metabolism of several non-small cell lung carcinoma (NSCLC) cell lines and could show that, NSCLC display distinct glycolytic metabolism. Genetic and pharmacological perturbation of glycolysis was selectively toxic to NSCLCs with high rates of glycolysis. Furthermore, high expression of hexokinase-2, localized at the mitochondria, was a feature of the NSCLCs dependent on glucose catabolism. Our study provides evidence for quantitative metabolic diversity in NSCLCs and indicates that glucose metabolism provide differential prosurvival benefits to NSCLCs.

来源:Hazardous Substances Data Bank (HSDB)

代谢

为了观察不同浓度的双酚A（BPA）对体外培养的大鼠支持细胞（Sertoli细胞）葡萄糖代谢和乳酸脱氢酶（LDH）表达的影响，并探讨BPA诱导男性不育的机制。我们使用两步酶消化法从雄性Wistar大鼠中分离出支持细胞，并构建了初级支持细胞体系，随后进行免疫组化FasL染色。我们将支持细胞随机分为对照组（在无血清最低必需培养基MEM中添加二甲基亚砜DMSO培养）和三个实验组（分别在MEM加DMSO中用100纳米摩尔/升、10微摩尔/升和1毫摩尔/升的BPA处理）。处理48小时后，我们通过CCK-8实验测量细胞增殖，通过核磁共振光谱法确定代谢物浓度，并通过RT-PCR和Western blot检测支持细胞中LDH的表达。分离出的支持细胞的纯度为（96.05 ± 1.28）%（n = 10）。与对照组相比，100纳米摩尔/升、10微摩尔/升和1毫摩尔/升BPA组支持细胞的增殖没有显著变化（分别为[98 ± 8]%，[96 ± 3]%，和[95 ± 3]%，P > 0.05），但10微摩尔/升和1毫摩尔/升BPA组的细胞内葡萄糖浓度显著降低（分别为[3.89 ± 0.07]对[3.36 ± 0.24]和[3.04 ± 0.21]皮摩尔/细胞，P < 0.05）和乳酸浓度（分别为[0.43 ± 0.06]对[0.29 ± 0.05]和[0.20 ± 0.03]皮摩尔/细胞，P < 0.05）。随着BPA浓度的增加，LDH mRNA的表达降低，而LDH蛋白的表达仅在1毫摩尔/升BPA组中降低（P < 0.05）。高浓度的BPA降低支持细胞中LDH的表达，并改变葡萄糖代谢，因此可能减少为生殖细胞提供的乳酸，损害精子生成。

To observe the influence of different concentrations of bisphenol A (BPA) on glucose metabolism and lactate dehydrogenase (LDH) expression in rat Sertoli cells in vitro and investigate the mechanisms of BPA inducing male infertility. Using two-step enzyme digestion, we isolated Sertoli cells from male Wistar rats and constructed a primary Sertoli cell system, followed by immunohistochemical FasL staining. We randomly divided the Sertoli cells into a control group to be cultured in the serum-free minimal essential medium (MEM) plus dimethyl sulfoxide (DMSO) and three experimental groups to be treated with 100 nmol/L, 10 umol/L, and 1 mmol/L BPA, respectively, in the MEM plus DMSO. After 48 hours of treatment, we measured the proliferation of the cells by CCK-8 assay, determined the concentrations of metabolites by NMR spectroscopy, and detected the expression of LDH in the Sertoli cells by RT-PCR and Western blot. The purity of the isolated Sertoli cells was (96.05 +/- 1.28)% (n = 10). Compared with the control group, the 100 nmol/L, 10 umol/L, and 1 mmol/L BPA groups showed no remarkable changes in the proliferation of Sertoli cells ([98 +/- 8]%, [96 +/- 3]%, and [95 +/- 3]%, P >0.05), but the 10 umol/L and 1 mmol/L of BPA groups exhibited significantly decreased concentrations of intracellular glucose ([3.89 +/- 0.07] vs [3.36 +/- 0.24] and [3.04 +/- 0.21] pmol/cell, P <0.05) and lactate ([0.43 +/- 0.06] vs [0.29 +/- 0.05] and [0.20 +/- 0.03] pmol/cell, P <0.05). The expression of LDH mRNA was decreased with the increased concentration of BPA, while that of LDH protein reduced only in the 1 mmol/L BPA group (P <0.05). High-concentration BPA decreases the expression of LDH and alters glucose metabolism in Sertoli cells, and therefore may reduce the provision of lactate for germ cells and impair spermatogenesis.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

葡萄糖形成无色晶体或白色颗粒粉末。它用于糖果、婴儿食品、医药、酿造和酿酒、焦糖着色、烘焙和罐头食品，通过厌氧发酵产生甲烷的来源，通过发酵产生某些氨基酸的来源。葡萄糖的主要工业发酵用途是生产作为氧合剂或辛烷增强剂的燃料乙醇。葡萄糖氢化成山梨醇，用于各种食品和非食品应用。液体葡萄糖是可可糖浆的成分，它被用作片剂粘合剂和包衣剂，以及作为药丸提取物的稀释剂；它已取代甘油用于许多药物制剂。有时，当通过胃进食不可能时，它可以通过直肠给药作为食物。它不应替代葡萄糖用于静脉注射。人类暴露和毒性：成年人的正常空腹血糖值为80至120 mg/dL；真正的葡萄糖为65至100 mg/dL。当血糖值超过120（高血糖）时，应怀疑糖尿病，并通过减少碳水化合物耐受性的证据来确认。高血糖和降低葡萄糖耐受性在糖尿病（高达500 mg/dL）和肾上腺、垂体和甲状腺功能亢进中可见。低血糖，血糖值<60 mg/dL和增加葡萄糖耐受性，在胰岛素过量、胰高血糖素缺乏和多种内分泌腺功能减退时遇到。将5%溶液注射到表浅颞动脉中，导致眼睑水肿、眼球突出、无法移动眼睛、软组织坏死和角膜混浊。在一侧眼睛中，观察到脉络膜一半的广泛萎缩。母亲高血糖可能导致胎儿乳酸产生增加，从而导致代谢性酸中毒。胎儿葡萄糖过多可能会刺激胎儿氧化代谢，增加胎儿葡萄糖和乳酸进入并刺激胎儿氧气消耗。动物研究：用葡萄糖和牛奶替代品以2:1的比例喂养的小牛，而不是推荐的1:1，表现出抑郁和腹泻，有四只动物在夜间死亡。尸检发现包括脱水、眼睛凹陷、充血的瘤胃粘膜和扩张的肠子。肺部充血，膀胱扩张，尿液中葡萄糖含量超过0.5 g/dL。研究发现，高血糖增加了颤抖的阈值，而低血糖降低了兔子的阈值。在小白鼠的发展研究中发现，母系糖尿病和高葡萄糖体外诱导DNA损伤并通过氧化应激激活DNA损伤反应，这可能导致糖尿病相关胚胎病的发病机制。

IDENTIFICATION AND USE: Glucose forms colorless crystals or white granular powder. It is used in confectionary, infant foods, medicine, brewing and wine making, caramel coloring, baking and canning, source of methane by anaerobic fermentation, source of certain amino acids by fermentation. A principal industrial fermentation use of glucose is for the production of fuel ethanol as an oxygenate or octane enhancer. Glucose is hydrogenated to sorbitol for use in various food and nonfood applications. Liquid glucose is an ingredient of Cocoa Syrup, It is used as a tablet binder and coating agent, and as a diluent in pilular extracts; it has replaced glycerin in many pharmaceutical preparations. It is sometimes given per rectum as a food in cases when feeding by stomach is impossible. It should not be used in the place of dextrose for intravenous injection. HUMAN EXPOSURE AND TOXICITY: Normal fasting blood-sugar values for adults are 80 to 120 mg/dL; true glucose is 65 to 100 mg/dL. When the blood-sugar values exceed 120 (hyperglycemia), diabetes mellitus should be suspected and can be confirmed by evidence of diminished carbohydrate tolerance. Hyperglycemia and decreased glucose tolerance are seen in diabetes mettilus (to 500 mg/dL) and hyperactivity of the adrenal, pituitary, and thyroid glands. Hypoglycemia, with a blood-sugar value of <60 mg/dL and increased glucose tolerance, is encountered in insulin overdose, glucagon deficiencies, and hypoactivity of various endocrine glands. Injection of 5% soln into superficial temporal artery caused edema of eyelids, protrusion of eye, inability to move eye, necrosis of soft tissues and opacification of cornea. In one of the eyes, extensive atrophy of temporal half of choroid was observed. Maternal hyperglycemia may lead to an increased fetal lactate production resulting in metabolic acidosis. Fetal glucose excess may stimulates fetal oxidative metabolism with increases in fetal glucose and lactate entry and stimulation of fetal oxygen consumption. ANIMAL STUDIES: Calves fed with a mixture of glucose and milk substitute in the ratio of 2:1 instead of the recommended 1:1 showed depression and diarrhea, with four animals dying overnight. The post-mortem findings included dehydration, sunken eyes, congested abomasal mucosa, and distended intestines. The lungs were congested and the urinary bladder distended, the urine having a glucose content of over 0.5 g/dL. It was found that hyperglycemia increases the threshold for shivering, whereas hypoglycemia lowers the threshold on rabbits. In developmental studies in mice it was found that maternal diabetes and high glucose in vitro induce DNA damage and activates DNA damage response through oxidative stress, which may contribute to the pathogenesis of diabetes-associated embryopathy.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

该物质可以通过摄入被身体吸收。

The substance can be absorbed into the body by ingestion.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 相互作用

最近的研究表明，肉类摄入与糖尿病相关表型有关。然而，肉类摄入与葡萄糖和胰岛素稳态的关系是否会被与葡萄糖和胰岛素相关的基因所改变，目前尚不清楚。我们调查了在没有糖尿病的白人中，肉类摄入与基因型相互作用对空腹血糖和胰岛素浓度的影响。作为心脏和老龄化研究的基因组流行病学联盟一部分的十四项研究参与了此次分析。数据来源于多达50,345名参与者。通过研究内的线性回归和跨研究的固定效应荟萃分析，我们检查了1）加工肉类和未加工红肉摄入与空腹血糖和胰岛素浓度的关系；以及2）加工肉类和未加工红肉与空腹血糖或胰岛素抵抗相关的遗传风险评分对空腹血糖和胰岛素浓度的相互作用。在校正了可能的混杂因素（不包括体重指数BMI）后，加工肉类与较高的空腹血糖有关，未加工红肉与较高的空腹血糖和空腹胰岛素浓度有关。每天每增加50克加工肉类，空腹血糖就会高出0.021毫摩尔/升（95%置信区间：0.011, 0.030毫摩尔/升）。每天每增加100克未加工红肉，空腹血糖浓度就会高出0.037毫摩尔/升（95%置信区间：0.023, 0.051毫摩尔/升），空腹胰岛素浓度就会高出0.049自然对数皮摩尔/升（95%置信区间：0.035, 0.063自然对数皮摩尔/升）。在进一步校正BMI后，观察到的关联减弱，不再具有统计学意义。在对多个比较进行校正后，加工肉类与空腹胰岛素的关系未达到统计学意义。已知的会影响空腹血糖或胰岛素抵抗的遗传位点的观察关联并未受到影响。与肉类消费相关的较高空腹血糖和胰岛素浓度并未受到与葡萄糖和胰岛素相关的单核苷酸多态性指数的影响。

Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

近期研究表明，长期暴露于空气污染（AP）会对代谢综合征及其组成部分产生不利影响。在一项基于人群的研究中，我们调查了环境AP暴露与血糖（SG）之间的关系，研究对象包括血糖正常、空腹血糖受损（IFG）和糖尿病（DM）的人群。我们纳入了2001-2012年间131,882名受试者进行的1,063,887次SG测试。暴露数据包括SO2、NO2以及其他来自工业、交通和非人为来源的污染物的日平均水平。评估了人口统计、临床和药物购买数据。通过对数转换的SG水平进行分析，采用线性混合模型，并调整季节性变量和个人特征。 在血糖正常、IFG和DM的人群中，SG的增加（%增加[95% CI]）分别与测试前24至72小时测得的 每增加6.36 ?ppb相关（0.40% [0.31%; 0.50%]，0.56% [0.40%; 0.71%]，1.08% [0.86%; 1.29%]）；以及与测试前24小时测得的SO2每增加1.17 ?ppb相关（0.29% [0.22%; 0.36%]，0.20% [0.10%; 0.31%]，0.33% [0.14%; 0.52%]）。在DM人群中，使用二甲双胍治疗的患者的关联性最弱（SG增加0.56% [0.18%; 0.95%]）。结论是， 和SO2暴露与SG水平的小幅但显著增加有关。尽管发现DM患者对AP诱导的SG变化更为敏感，但二甲双胍治疗似乎具有保护作用。鉴于人们长期暴露于AP以及人口的广泛覆盖，即使是我们研究中发现的小幅关联，也可能与健康损害有关，并可能对公共卫生产生深远影响。

Recent studies demonstrated an adverse effect of chronic exposure to air pollution (AP) on metabolic syndrome and its components. In a population-based study, we investigated the association between exposure to ambient AP and serum glucose (SG), among subjects with normal glucose, impaired fasting glucose (IFG), and diabetes mellitus (DM).We included 1,063,887 SG tests performed in 131,882 subjects (years 2001-2012). Exposure data included daily levels of SO2, NO2 and other pollutants of industrial, traffic, and nonanthropogenic sources. Demographical, clinical, and medications purchase data were assessed. Log-transformed SG levels were analyzed by linear mixed models adjusted for seasonal variables and personal characteristics.SG increases (%increase [95% CI]), among subjects with normal glucose, IFG, and DM, respectively, were associated with 6.36 ?ppb increase of NO2 measured 24 to 72? hours before the test (0.40% [0.31%; 0.50%], 0.56% [0.40%; 0.71%], and 1.08% [0.86%; 1.29%]); and with 1.17?ppb increase of SO2 measured 24 ?hours before the test (0.29% [0.22%; 0.36%], 0.20% [0.10%; 0.31%], and 0.33% [0.14%; 0.52%]). Among DM population, weakest association was observed among patients treated with Metformin (0.56% increase in SG [0.18%; 0.95%]). In conclusion, NO2 and SO2 exposure is associated with small but significantly increased levels of SG. Although DM patients were found to be more susceptible to the AP induced SG variations, Metformin treatment seem to have a protective effect. Given the chronic lifetime exposure to AP and the broad coverage of the population, even small associations such as those found in our study can be associated with detrimental health effects and may have profound public health implications.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

母源性糖尿病引起的出生缺陷仍然是一个重要的健康问题。研究具有抗氧化性质和最小毒性的天然化合物对糖尿病胚胎病的影响可能有助于开发新的、安全的膳食补充剂。石榴汁中的主要多酚——安石榴苷，具有抗氧化、抗炎和抗肿瘤生成的特性，这表明安石榴苷对糖尿病胚胎病具有保护作用。在这里，我们研究了安石榴苷是否能减少高糖引起的中枢神经系统缺陷（NTDs），以及这种挽救作用是否通过阻断细胞应激和caspase活化实现。将8.5天大的小鼠胚胎在正常糖（5 mM）或高糖（16.7 mM）条件下培养24或36小时，并在存在或不存在10或20 uM安石榴苷的情况下。10 uM安石榴苷在高糖条件下轻微减少了NTD的形成；然而，20 uM安石榴苷显著抑制了高糖诱导的NTD形成。安石榴苷抑制了高糖诱导的脂质过氧化标志物4-羟基壬烯醛、硝基酪氨酸修饰蛋白和脂质过氧化物的产生。此外，安石榴苷通过抑制磷酸化蛋白激酶RNA样内质网激酶（p-PERK）、磷酸化肌醇需要蛋白-1alpha（p-IRE1alpha）、磷酸化真核起始因子2alpha（p-eIF2alpha）、C/EBP同源蛋白（CHOP）、结合免疫球蛋白蛋白（BiP）和x-box结合蛋白1（XBP1）mRNA的剪接，从而消除了内质网应激。此外，安石榴苷还抑制了高糖诱导的caspase 3和caspase 8的裂解。安石榴苷通过阻断细胞应激和caspase活化减少高糖诱导的NTD形成。这些观察结果提示安石榴苷补充剂可能减轻高血糖在发育胚胎中的致畸作用，并可能预防糖尿病引起的NTDs。

Maternal diabetes-induced birth defects remain a significant health problem. Studying the effect of natural compounds with antioxidant properties and minimal toxicities on diabetic embryopathy may lead to the development of new and safe dietary supplements. Punicalagin is a primary polyphenol found in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumorigenic properties, suggesting a protective effect of punicalagin on diabetic embryopathy. Here, we examined whether punicalagin could reduce high glucose-induced neural tube defects (NTDs), and if this rescue occurs through blockage of cellular stress and caspase activation. Embryonic day 8.5 (E8.5) mouse embryos were cultured for 24 or 36 hr with normal (5 mM) glucose or high glucose (16.7 mM), in presence or absence of 10 or 20 uM punicalagin. 10 uM punicalagin slightly reduced NTD formation under high glucose conditions; however, 20 uM punicalagin significantly inhibited high glucose-induced NTD formation. Punicalagin suppressed high glucose-induced lipid peroxidation marker 4-hydroxynonenal, nitrotyrosine-modified proteins, and lipid peroxides. Moreover, punicalagin abrogated endoplasmic reticulum stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1alpha (p-IRE1alpha), phosphorylated eukaryotic initiation factor 2alpha (p-eIF2alpha), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, punicalagin suppressed high glucose-induced caspase 3 and caspase 8 cleavage. Punicalagin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation. These observations suggest punicalagin supplements could mitigate the teratogenic effects of hyperglycemia in the developing embryo, and possibly prevent diabetes-induced NTDs.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

IL-6家族成员IL-6和纤毛神经营养因子（CNTF）已被证明能增加骨骼肌对葡萄糖的摄取和脂肪酸的氧化。然而，另一个家族成员，白血病抑制因子（LIF）的代谢效应尚未得到很好的描述。本研究调查了LIF对骨骼肌葡萄糖摄取和棕榈酸氧化以及信号传导的影响，实验中使用了体外孵育的小鼠比目鱼肌和EDL肌，这些肌肉来自肌肉特异性AMPKalpha2激酶失活、肌肉特异性SOCS3敲除以及瘦和高脂饮食小鼠。使用抑制剂来探究特定信号通路的作用。LIF以剂量（50-5,000 pM/l）和时间依赖性方式增加了肌肉对葡萄糖的摄取，在30分钟时间点达到最大效果。LIF增加了比目鱼肌和EDL中Akt Ser(473)的磷酸化（P），而AMPK Thr(172) P不受影响。使用小白菊内酯的孵育消除了LIF诱导的葡萄糖摄取和STAT3 Tyr(705) P，而使用LY-294002和wortmannin的孵育抑制了基础的和LIF诱导的葡萄糖摄取以及Akt Ser(473) P，表明JAK和PI 3-激酶信号对于LIF刺激的葡萄糖摄取是必需的。使用雷帕霉素和AZD8055的孵育表明，哺乳动物靶标雷帕霉素复合物（mTORC）2，而不是mTORC1，也对于LIF刺激的葡萄糖摄取是必需的。与CNTF不同，LIF刺激并未改变棕榈酸氧化。LIF刺激的葡萄糖摄取在来自肥胖胰岛素抵抗小鼠的EDL中得以维持，而比目鱼肌则发展出对LIF的抵抗。缺乏SOCS3和AMPKalpha2并未影响LIF刺激的葡萄糖摄取。总之，LIF通过一种可能涉及PI 3-激酶/mTORC2/Akt通路的机制急性增加了肌肉对葡萄糖的摄取，并且在肥胖胰岛素抵抗小鼠的EDL肌肉中并未受损。

Members of the IL-6 family, IL-6 and ciliary neurotrophic factor (CNTF), have been shown to increase glucose uptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member, leukemia inhibitory factor (LIF), are not well characterized. Effects of LIF on skeletal muscle glucose uptake and palmitate oxidation and signaling were investigated in ex vivo incubated mouse soleus and EDL muscles from muscle-specific AMPKalpha2 kinase-dead, muscle-specific SOCS3 knockout, and lean and high-fat-fed mice. Inhibitors were used to investigate involvement of specific signaling pathways. LIF increased muscle glucose uptake in dose (50-5,000 pM/l) and time-dependent manners with maximal effects at the 30-min time point. LIF increased Akt Ser(473) phosphorylation (P) in soleus and EDL, whereas AMPK Thr(172) P was unaffected. Incubation with parthenolide abolished LIF-induced glucose uptake and STAT3 Tyr(705) P, whereas incubation with LY-294002 and wortmannin suppressed both basal and LIF-induced glucose uptake and Akt Ser(473) P, indicating that JAK and PI 3-kinase signaling is required for LIF-stimulated glucose uptake. Incubation with rapamycin and AZD8055 indicated that mammalian target of rapamycin complex (mTORC)2, but not mTORC1, also is required for LIF-stimulated glucose uptake. In contrast to CNTF, LIF stimulation did not alter palmitate oxidation. LIF-stimulated glucose uptake was maintained in EDL from obese insulin-resistant mice, whereas soleus developed LIF resistance. Lack of SOCS3 and AMPKalpha2 did not affect LIF-stimulated glucose uptake. In conclusion, LIF acutely increased muscle glucose uptake by a mechanism potentially involving the PI 3-kinase/mTORC2/Akt pathway and is not impaired in EDL muscle from obese insulin-resistant mice.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

工作的目的是分析大鼠对葡萄糖溶液的消耗与其吸收之间的关系，并利用这一事实来评估非麻醉动物活体小肠的吸收能力。记录了禁食大鼠对200克/升葡萄糖溶液的消耗情况，在对照组中，以及在给予葡萄糖主动运输抑制剂根皮素后，或者在限制性应激后3小时。我们在数学模型上研究了可能影响大鼠葡萄糖消耗时间动态的因素的相对作用。观察到在根皮素（1毫摩尔）存在时，葡萄糖消耗速率降低，而在应激后增加。建模结果与实验数据一致，并显示葡萄糖溶液的消耗速率在很大程度上取决于小肠的运输活性，而不是溶液中的葡萄糖浓度，或者胃排空的底物调节。分析完整大鼠对葡萄糖溶液消耗的动态可能被认为是评估自然条件下小肠吸收能力的有前景的方法之一。

The aim of the work is to analyze the relationship between consumption of glucose solution by rats and its absorption, and to use this fact for assessment of the absorptive capacity of the small intestine in non anesthetized animals in vivo. Consumption of glucose solution (200 g/L) by fasted rats was recorded in the control, and after administration of phloridzin--inhibitor of glucose active transport- or 3 hours after the restriction stress. On the mathematical model we studied the relative role of factors that can influence the temporal dynamics of glucose consumption by rats. The rate of glucose consumption was observed being decreased in the presence of phloridzin (1 mM), and be increased after the stress. The results of modeling are consistent with the experimental data and show that the rate of consumption of glucose solutions considerably more depends on the transport activity of the small intestine than on glucose concentration in the solution, or on the substrate regulation of the stomach emptying. Analysis of dynamics of consumption of glucose solution by intact rats may be considered as one of promising approaches to assessing the absorptive capacity of the small intestine under natural conditions.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

促进扩散涉及胎盘内的载体物质，它有助于提高转移速率，超过预期的水平...葡萄糖显然是以这种方式转移的。...不需要代谢能量，且转移是沿着浓度梯度的方向进行的。

Facilitated diffusion involves carrier substance within placenta, which acts to incr rate of transfer beyond that which would be expected... glucose is apparently transferred in this manner. ...No metabolic energy may be required, & transfer is in direction of concn gradient.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当过量葡萄糖静脉注射后，血糖值通常在一到两个小时内恢复正常，大部分过量葡萄糖通过肾脏排出，其中40%的葡萄糖通过透析进入组织，少量通过氧化分解。

When excesses are given IV blood sugar values usually return near normal within an hour or two, most of excess having been eliminated through kidneys, & CA 40% dialyzes into tissues with small amt destroyed by oxidation.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  29400000
• 危险性防范说明：
  P264,P302+P352,P304+P340,P305+P351+P338,P332+P313,P337+P313
• 危险性描述：
  H315,H319,H335
• 储存条件：
  密封保存，应储存在阴凉干燥的仓库中。

SDS

Name:	D-(+)-Altrose 99% Material Safety Data Sheet
Synonym:	None known
CAS:	1990-29-0

Section 1 - Chemical Product MSDS Name:D-(+)-Altrose 99% Material Safety Data Sheet
Synonym:None known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
1990-29-0	D-(+)-Altrose	99	217-870-4

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 1990-29-0: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Powder
Color: off-white
Odor: none reported
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 106.00 - 108.00 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C6H12O6
Molecular Weight: 180.16

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 1990-29-0 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
D-(+)-Altrose - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 1990-29-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 1990-29-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 1990-29-0 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用

13C6-葡萄糖已被用作：

• 作为从头合成脂肪酸(FA)的示踪剂，分析稳定同位素示踪剂在重组蛋白生产中的作用；
• 作为示踪介质中分析稳定同位素示踪剂的组分；
• 用于重组蛋白生产的基本培养基中；
• 用于悬浮细胞。

生物活性

D-Glucose-13C6（葡萄糖-13C6）是一种追踪与葡萄糖相关的合成分解代谢的示踪剂，它是一种低成本的替代品。其显著优势在于天然葡萄糖的第六种同位素实际上具有零自然丰度，这有助于在输注液中使用小于 1% 标记的葡萄糖进行同位素异构体分析。

反应信息

• 作为反应物：
  描述：

  2,3,4,5,6-pentahydroxy-hexanal 在 aluminum(III) sulphate octadecahydrate 、 草酸 、 溴化胆碱 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 1.5h， 以67.1%的产率得到5-(溴甲基)呋喃-2-甲醛
  参考文献：
  名称：

  一种5-卤代甲基糠醛的制备方法

  摘要：

  本发明公开了一种5‑卤代甲基糠醛的制备方法，包括如下步骤：(1)将原料、氯化胆碱/溴化胆碱、作为氢键供体的有机酸、金属盐和二氯乙烷加入反应器中，于80‑150℃搅拌反应5‑300min，获得由上层和下层组成的反应相，该下层为低共熔溶剂相，该上层为二氯乙烷相；(2)将上述低共熔溶剂相经二氯乙烷萃取和分离纯化，获得含有5‑卤代甲基糠醛的产物。本发明选用的原料来源更加广泛，廉价易得；反应条件温和，反应产率高；为今后5‑卤代甲基糠醛及其下游产物研究提供了一种新颖的思路。

  公开号：

  CN112279825B
• 作为产物：
  描述：

  2-己酮醣 在 Sn/deAl-β zeolite CP814E, 0.03 mmol/g Sn, deAl - dealuminated 作用下， 以 水 为溶剂， 反应 2.0h， 生成 2,3,4,5,6-pentahydroxy-hexanal
  参考文献：
  名称：

  Productive sugar isomerization with highly active Sn in dealuminated β zeolites

  摘要：

  一种耐水路易斯酸催化剂通过在异丙醇中回流方式合成，其方法是将SnIV插枝到去铝沸石（BEA（β）拓扑）上。这种合成方法使得能够生产高度活性的Snβ型催化剂，而无需长时间的水热合成或氟化氢，同时还使用便宜的Sn前驱体、工业上可获得的β沸石和标准催化剂合成单元操作。对最佳催化剂的广泛表征显示，在沸石基体中高度分散的Sn（XRD、29Si MAS NMR和1H MAS NMR），而未形成SnO2（XRD和UV-Vis）。该催化剂用于模型糖异构化反应，例如将葡萄糖转化为果糖。催化活性证明是纯粹的异相，并且催化剂在回收和再使用过程中没有显著的活性损失。报告的异构化产量超过每kg催化剂每小时4kg产物，且Sn负载显著低，相应地表现出异常高的周转频率，即在110°C时每小时每个Sn达到500个周期，这超出了原水热合成Snβ的每个Sn的活性。

  DOI：

  10.1039/c3gc41239c
• 作为试剂：
  描述：

  2-(溴甲基)吡啶氢溴酸盐 在 glucose dehydrogenase 、 2,3,4,5,6-pentahydroxy-hexanal 、 nicotinamide adenine dinucleotide 、 sodium hydride 、 Baeyer–Villiger monooxygenase 145 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  扩展 Baeyer-Villiger 和黄素单加氧酶生物催化剂的工具箱，用于亚砜的对映异构绿色合成

  摘要：

  两种新的单加氧酶生物催化剂，Baeyer-Villiger 单加氧酶 BVMO145 和来自 Almac 库的黄素单加氧酶 FMO401，被发现可以在温和和绿色条件下催化带有 N-杂环取代基的硫化物对映异构氧化成亚砜。生物催化剂 BVMO145 提供 ( S )-亚砜，而黄素单加氧酶 FMO401 提供 ( R )-亚砜，具有良好的转化率和高 ee。

  DOI：

  10.1039/d4gc02657h

文献信息

• [EN] BENZAMIDE OR BENZAMINE COMPOUNDS USEFUL AS ANTICANCER AGENTS FOR THE TREATMENT OF HUMAN CANCERS<br/>[FR] COMPOSÉS BENZAMIDE OU BENZAMINE À UTILISER EN TANT QU'ANTICANCÉREUX POUR LE TRAITEMENT DE CANCERS HUMAINS
  申请人：UNIV TEXAS

  公开号：WO2017007634A1

  公开（公告）日：2017-01-12

  The described invention provides small molecule anti-cancer compounds for treating tumors that respond to cholesterol biosynthesis inhibition. The compounds selectively inhibit the cholesterol biosynthetic pathway in tumor-derived cancer cells, but do not affect normally dividing cells.

  所描述的发明提供了用于治疗对胆固醇生物合成抑制作出反应的肿瘤的小分子抗癌化合物。这些化合物选择性地抑制肿瘤来源的癌细胞中的胆固醇生物合成途径，但不影响正常分裂的细胞。
• [EN] TARGETED DELIVERY AND PRODRUG DESIGNS FOR PLATINUM-ACRIDINE ANTI-CANCER COMPOUNDS AND METHODS THEREOF<br/>[FR] ADMINISTRATION CIBLÉE ET CONCEPTIONS DE PROMÉDICAMENTS POUR COMPOSÉS ANTICANCÉREUX À BASE DE PLATINE ET D'ACRIDINE ET MÉTHODES ASSOCIÉES
  申请人：WAKE FOREST SCHOOL OF MEDICINE

  公开号：WO2013033430A1

  公开（公告）日：2013-03-07

  Acridine containing cispiaiin compounds have been disclosed that show greater efficacy against cancer than other cisplatin compounds. Methods of delivery of those more effective eisp!aiin compounds to the nucleus in cancer ceils is disclosed using one or more amino acids, one or more sugars, one or more polymeric ethers, C i^aikylene-phenyl-NH-C(0)-R.15, folic acid, av03 iniegriii RGD binding peptide, tamoxifen, endoxifen, epidermal growth factor receptor, antibody conjugates, kinase inhibitors, diazoles, triazol.es, oxazoies, erlotinib, and/or mixtures thereof; wherein R]§ is a peptide.

  含有环丙啶结构的吖啶类化合物已被披露，显示出比其他顺铂类化合物更有效地对抗癌症。使用一种或多种氨基酸、一种或多种糖、一种或多种聚合醚、C i^aikylene-phenyl-NH-C(0)-R.15、叶酸、av03整合RGD结合肽、他莫昔芬、恩多西芬、表皮生长因子受体、抗体结合物、激酶抑制剂、二唑类化合物、三唑类化合物、噁唑类化合物、厄洛替尼和/或它们的混合物将这些更有效的吖啶类化合物传递到癌细胞核中的方法被披露；其中R]§是一个肽。
• N-type calcium channel blockers
  申请人：Pajouhesh Hassan

  公开号：US20050165065A1

  公开（公告）日：2005-07-28

  The invention relates to novel 3-amino pyrrolidine derivatives, as well as methods for modulating calcium channel activity and for treating conditions associated with calcium channel function. In particular, the compounds generally contain at least one benzhydril moiety, and are useful in treating conditions which benefit from blocking calcium ion channels.

  这项发明涉及新型3-氨基吡咯烷衍生物，以及调节钙通道活性和治疗与钙通道功能相关疾病的方法。具体来说，这些化合物通常至少含有一个苯基甲酰基团，可用于治疗受益于阻断钙离子通道的疾病。
• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS
  申请人：Arora Nidhi

  公开号：US20120015962A1

  公开（公告）日：2012-01-19

  Compounds of the formula I or II: wherein X, m, Ar, R 1 and R 2 are as defined herein. The subject compounds are useful for treatment of IRAK-mediated conditions.

  式I或II的化合物： 其中X，m，Ar，R1和R2如本文所定义。所述化合物对于治疗IRAK介导的疾病是有用的。