二氯乙酸钠

二氯乙酸钠用途

Sodium dichloroacetate 是癌细胞线粒体中的一种代谢调节剂,具有抗癌活性。Sodium dichloroacetate 抑制 PDHK,从而导致肿瘤微环境中的乳酸减少。Sodium dichloroacetate 增加活性氧 (ROS) 的产生并促进癌细胞凋亡,还可作为 NKCC 抑制剂。

点击显示

二氯乙酸钠名称

[ CAS 号 ]:
2156-56-1

[ 中文名 ]:
二氯乙酸钠

[ 英文名 ]:
Sodium Dichloroacetate

[英文别名 ]:

Acetic acid, 2,2-dichloro-, sodium salt (1:1)
EINECS 218-461-3
MFCD00070489
Cpc 211
sodium salt of dichloroacetate
Sodium dichloroacetate [USAN]
Natriumdichloracetat
dichloroacetate de sodium
ACETIC ACID,DICHLORO-,SODIUM SALT
Sodium dichloroacetate

二氯乙酸钠生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> PDHK

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

信号通路 >> 跨膜转运 >> NKCC

[ 靶点 ]

PDHK; Reactive oxygen species (ROS); Apoptosis; NKCC[1]

[体外研究]

二氯乙酸钠增加线粒体中ROS的生成。二氯乙酸钠通过促进氧化代谢而促进ROS生成,从而影响细胞生长和活力。二氯乙酸钠对多发性骨髓瘤细胞活力、细胞周期阻滞和凋亡细胞死亡的影响与丙酮酸脱氢酶(PDK)抑制、丙酮酸脱氢酶(PDH)活性恢复有关,促进氧化代谢与细胞内ROS增加有关,这取决于二氯乙酸钠剂量。二氯乙酸钠协同抑制大鼠VM－M3胶质母细胞瘤细胞氧化应激的作用。二氯乙酸钠处理的癌细胞中ROS水平升高与细胞色素c表达增加相关的凋亡诱导有关。二氯乙酸钠引起ROS依赖性T细胞分化[1]。

[体内研究]

在二氯乙酸钠处理的性腺完整和去势雄性大鼠中,NKCC1 RNA的表达水平显著降低,而在性腺完整和去势雌性二氯乙酸钠处理的大鼠中,没有这种作用[1]。单剂量二氯乙酸钠可显著提高Wistar雄性大鼠24小时的排尿量,其增加的排尿量与NKCC2的抑制有关。与正常雄性大鼠相比,正常雌性大鼠肾脏中NKCC2的含量更丰富,Sprague-Dawley雌性大鼠的转运蛋白密度更高[1]。给药5、20和100mg/kg的初生雄性大鼠口服二氯乙酸钠的生物利用度显著低于GSTζ耗尽组(分别为10%、13%、81%和31%、75%、100%)。GSTζ耗竭大鼠肝脏中二氯乙酸钠的提取具有线性动力学,但在较高剂量时,随着代谢饱和度的增加,提取率降低[1]。

[参考文献]

[1]. Stakišaitis D, et al. The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo. Cancers (Basel). 2019 Aug 20;11(8). pii: E1210.

二氯乙酸钠物理化学性质

[ 沸点 ]:
194ºC at 760mmHg

[ 熔点 ]:
198 °C (dec.)(lit.)

[ 分子式 ]:
C₂HCl₂NaO₂

[ 分子量 ]:
150.924

[ 精确质量 ]:
149.925125

[ PSA ]:
40.13000

[ 外观性状 ]:
白色粉末

[ 蒸汽压 ]:
0.196mmHg at 25°C

[ 储存条件 ]:
Desiccate at RT

[ 水溶解性 ]:
soluble in cold water

二氯乙酸钠MSDS

详细MSDS(安全技术说明书)

二氯乙酸钠毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AG9275000

CHEMICAL NAME :: Acetic acid, dichloro-, sodium salt

CAS REGISTRY NUMBER :: 2156-56-1

LAST UPDATED :: 199801

DATA ITEMS CITED :: 13

MOLECULAR FORMULA :: C2-H-Cl2-O2.Na

MOLECULAR WEIGHT :: 150.92

WISWESSER LINE NOTATION :: QVYGG &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5281 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 4845 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >3 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 30425 mg/kg/12W-C

TOXIC EFFECTS :: Brain and Coverings - changes in brain weight Endocrine - changes in adrenal weight Kidney, Ureter, Bladder - changes in bladder weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 45500 mg/kg/13W-I

TOXIC EFFECTS :: Endocrine - hypoglycemia Liver - changes in liver weight Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2450 mg/kg/7W-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes in urine composition Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other Enzymes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 61 gm/kg/12W-C

TOXIC EFFECTS :: Peripheral Nerve and Sensation - recording from peripheral motor nerve Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in testicular weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 4550 mg/kg/13W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - food intake (animal) Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 164 gm/kg/1Y-C

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 182 gm/kg

SEX/DURATION :: male 13 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4375 mg/kg

SEX/DURATION :: male 10 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2188 mg/kg

SEX/DURATION :: male 10 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

MUTATION DATA

TYPE OF TEST :: Mutation in microorganisms

TEST SYSTEM :: Bacteria - Salmonella typhimurium

DOSE/DURATION :: 5 ug/plate

REFERENCE :: AJCNAC American Journal of Clinical Nutrition. (American Soc. for Clinical Nutrition, Inc., 9650 Rockville Pike, Bethesda, MD 20814) V.2- 1954- Volume(issue)/page/year: 33,1179,1980

点击显示

二氯乙酸钠安全信息

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Warning

[ 危害声明 ]:
H315-H319-H335-H351

[ 警示性声明 ]:
P261-P281-P305 + P351 + P338

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xi:Irritant;

[ 风险声明 (欧洲) ]:
R36/37/38

[ 安全声明 (欧洲) ]:
S26-S37/39

[ 危险品运输编码 ]:
2811

[ WGK德国 ]:
2

[ RTECS号 ]:
AG9275000

[ 海关编码 ]:
2942000000

二氯乙酸钠上下游产品

二氯乙酸钠上游产品

二氯乙酸钠下游产品

二氯乙酸钠海关

[ 海关编码 ]: 2942000000

二氯乙酸钠文献

Dual-targeting of aberrant glucose metabolism in glioblastoma.

J. Exp. Clin. Cancer Res 34 , 14, (2015)

Glioblastoma (GBM) is the most common and malignant primary brain tumor. In contrast to some other tumor types, aberrant glucose metabolism is an important component of GBM growth and chemoresistance....

A Korean female patient with thiamine-responsive pyruvate dehydrogenase complex deficiency due to a novel point mutation (Y161C)in the PDHA1 gene.

J. Korean Med. Sci. 21 , 800-4, (2006)

Pyruvate dehydrogenase complex (PDHC) deficiency is mostly due to mutations in the X-linked E1alpha subunit gene (PDHA1). Some of the patients with PDHC deficiency showed clinical improvements with th...

Sensitization of Glioblastoma Cells to Irradiation by Modulating the Glucose Metabolism.

Mol. Cancer Ther. 14 , 1794-804, (2015)

Because radiotherapy significantly increases median survival in patients with glioblastoma, the modulation of radiation resistance is of significant interest. High glycolytic states of tumor cells are...

更多文献