丙戊酸_MSDS_用途_密度_丙戊酸CAS号【99-66-1】

Valproic acid 是一种 HDAC 抑制剂,IC50 值为 0.5-2 mM,抑制 HDAC1 的活性,(IC50,400 μM),同时可诱导 HDAC2 的降解；Valproic acid sodium salt 可用于癫痫、双相情感障碍和偏头痛等的研究。

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[ 描述 ]:

Valproic acid 是一种 HDAC 抑制剂,IC50 值为 0.5-2 mM,抑制 HDAC1 的活性,(IC50,400 μM),同时可诱导 HDAC2 的降解；Valproic acid sodium salt 可用于癫痫、双相情感障碍和偏头痛等的研究。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

信号通路 >> 细胞周期/DNA损伤 >> HDAC

信号通路 >> 表观遗传学 >> HDAC

信号通路 >> 自噬 >> 自噬

天然产物 >> 酸和醛

研究领域 >> 癌症

[ 靶点 ]

HDAC1:400 μM (IC50)

HDAC:0.5-2 mM (IC50)

HDAC2

Autophagy

Mitophagy

[体外研究]

丙戊酸分别在24和72小时抑制生长剂量和时间依赖性,IC50分别为10和4mM。丙戊酸显着减弱总HDAC,细胞溶质和核HDAC的活性。丙戊酸增加HeLa细胞中乙酰化组蛋白3的形式。丙戊酸(1-3mM)诱导G1期阻滞,而10mM丙戊酸显着诱导HeLa细胞中细胞周期的G2/M期阻滞。此外,丙戊酸在24小时时以剂量依赖性方式增加HeLa细胞中亚G1细胞的百分比[1]。丙戊酸抑制VEGF,VEGFR2和bFGF的mRNA和蛋白质表达。丙戊酸抑制HDAC1的蛋白表达,增加组蛋白H3乙酰化,并增强高乙酰化组蛋白H3在VEGF启动子上的积累[2]。丙戊酸处理导致原代小鼠肝细胞中磷酸化AMPK/ACC水平增加。丙戊酸处理后ACC的磷酸化是AMPK依赖性的。丙戊酸抑制小鼠肝核提取物和人重组HDAC1的脱乙酰酶活性,而丙戊酸的代谢产物,只有2-烯-丙戊酸和4-烯-丙戊酸降低脱乙酰酶活性[4]。

[体内研究]

丙戊酸(500mg/kg,ip)抑制移植Kasumi-1细胞的小鼠的肿瘤生长和血管生成。在实验结束时,丙戊酸组的IR率为57.25％[2]。丙戊酸(350 mg/kg,ip)比对照动物表现出更多的社会调查和打斗[3]。

[激酶实验]

使用半胱天冬酶-3，-8和-9比色测定试剂盒分别评估胱天蛋白酶-3，-8和-9的活性。简而言之，将60-mm培养皿中的1×10 6个细胞与10mM丙戊酸一起温育24小时。然后将细胞在PBS中洗涤并悬浮在试剂盒提供的5倍体积的裂解缓冲液中。使用Bradford方法测定蛋白质浓度。含有50μg总蛋白的上清液用于测定胱天蛋白酶-3，-8和-9活性。将上清液加入96孔微量滴定板中的每个孔中，其中DEVD-pNA，IETD-pNA或LEHD-pNA作为半胱天冬酶-3，-8和-9底物，并将板在37℃温育1小时。使用酶标仪在405nm处测量每个孔的光密度。胱天蛋白酶-3，-8和-9的活性以任意吸光度单位表示。

[细胞实验]

简而言之，将5×10 5个细胞接种在96孔微量滴定板中用于MTT测定。在指定剂量的丙戊酸暴露指定时间后，将MTT溶液[20mL：2mg / mL在磷酸盐缓冲盐水（PBS）中]加入96孔板的每个孔中。将板另外在37℃下孵育3小时。通过移液将培养基从培养板中取出，并向每个孔中加入200mL DMSO以溶解甲crystals晶体。使用酶标仪在570nm下测量光密度。

[动物实验]

在BALB / c裸鼠上进行脾切除术。脾切除后一周，小鼠接受全身照射，剂量为4Gy的137Cs。在照射后48-72小时，在右腋窝区域向小鼠皮下植入Kasumi-1细胞（2×10 7个细胞/小鼠，0.15-0.2mL）。小鼠随机分为两组，丙戊酸（n = 6）和对照组（n = 6）。当肿瘤在植入后10天大小为200mm 3时，每天腹膜内注射0.2mL丙戊酸（500mg / kg体重）或0.2mL盐水。将丙戊酸以25mg / mL的浓度溶解在盐水中。每三天测量肿瘤的最长直径（a）和最短直径（b），并根据下式计算肿瘤体积（TV）：TV = 1/2×a×b2。注射两周后，通过颈脱位处死小鼠并取出肿瘤块用于以下实验。

[参考文献]

[1]. Han BR, et al. Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013 Dec;30(6):2999-3005.

[2]. Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.

[3]. Cohen OS, et al. Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats. Int J Dev Neurosci. 2013 Dec;31(8):740-50.

[4]. Avery LB, et al. Valproic Acid Is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice. Mol Pharmacol. 2014 Jan;85(1):1-10.

[5]. Valproic acid, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001 Sep 28;276(39):36734-41.

[相关活性小分子]

[ 密度 ]:
0.9±0.1 g/cm3

[ 沸点 ]:
220.0±0.0 °C at 760 mmHg

[ 熔点 ]:
120 - 130ºC

[ 分子式 ]:
C₈H₁₆O₂

[ 分子量 ]:
144.211

[ 闪点 ]:
111.1±0.0 °C

[ 精确质量 ]:
144.115036

[ PSA ]:
37.30000

[ LogP ]:
2.72

[ 外观性状 ]:
透明液体

[ 蒸汽压 ]:
0.0±0.9 mmHg at 25°C

[ 折射率 ]:
1.435

[ 储存条件 ]:
库房通风低温干燥,与氧化剂分开存放

[ 水溶解性 ]:
slightly soluble

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YV7875000

CHEMICAL NAME :: Valeric acid, 2-propyl-

CAS REGISTRY NUMBER :: 99-66-1

BEILSTEIN REFERENCE NO. :: 1750447

LAST UPDATED :: 199712

DATA ITEMS CITED :: 43

MOLECULAR FORMULA :: C8-H16-O2

MOLECULAR WEIGHT :: 144.24

WISWESSER LINE NOTATION :: QVY3&3

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 375 mg/kg

TOXIC EFFECTS :: Cardiac - pulse rate increase, without fall in BP Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - cyanosis

REFERENCE :: CCMDC7 Critical Care Medicine. (Williams & Wilkins, 428 E. Preston Street, Baltimore, MD 21202) V.1- 1973- Volume(issue)/page/year: 21,299,1993

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 412 mg/kg

TOXIC EFFECTS :: Behavioral - coma Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 20,55,1996

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 10500 mg/kg/30W-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of endocrine pancreas Gastrointestinal - nausea or vomiting

REFERENCE :: AJDCAI American Journal of Diseases of Children. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-80(3), 1911-50; V.100- 1960- Volume(issue)/page/year: 138,912,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 21 mg/kg/2D-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Nutritional and Gross Metabolic - other changes

REFERENCE :: NEURAI Neurology. (Modern Medicine Pub., Inc., 1 E. First St., Duluth, MN 55802) V.1- 1951- Volume(issue)/page/year: 37,886,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 1800 mg/kg/60D

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of endocrine pancreas Gastrointestinal - nausea or vomiting

REFERENCE :: LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,1196,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 13333 ug/kg/D-I

TOXIC EFFECTS :: Behavioral - sleep

REFERENCE :: NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 301,435,1979

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 670 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea

REFERENCE :: FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 2,327,1964

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1098 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #78785

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 470 mg/kg

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

REFERENCE :: CHTPBA Chimica Therapeutica. (Paris, France) V.1-8, 1965-73. For publisher information, see EJMCA5. Volume(issue)/page/year: 3,430,1968

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 860 mg/kg

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

REFERENCE :: 85GNAW "Pharmacodynamie de l'Acide Dipropylacetique (ou Propyl-2-Pentanoique) et de ses Amides," Carraz, G., Imprimerie Eymond, 1968 Volume(issue)/page/year: -,38,1968

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 1200 mg/kg

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

REFERENCE :: 85GNAW "Pharmacodynamie de l'Acide Dipropylacetique (ou Propyl-2-Pentanoique) et de ses Amides," Carraz, G., Imprimerie Eymond, 1968 Volume(issue)/page/year: -,39,1968

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 824 mg/kg

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

REFERENCE :: 85GNAW "Pharmacodynamie de l'Acide Dipropylacetique (ou Propyl-2-Pentanoique) et de ses Amides," Carraz, G., Imprimerie Eymond, 1968 Volume(issue)/page/year: -,39,1968 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5480 mg/kg

SEX/DURATION :: female 1-39 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

REFERENCE :: AEPEDI Anales Espanoles de Pediatria. (Asociacion Espanola de Pediatria, Apartado 1176, 28028 Madrid, Spain) V.1- 1968- Volume(issue)/page/year: 39,19,1993

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 720 mg/kg

SEX/DURATION :: female 1-90 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

REFERENCE :: CPEDAM Clinical Pediatrics (Philadelphia). (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1962- Volume(issue)/page/year: 22,336,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6525 mg/kg

SEX/DURATION :: female 26 week(s) pre-mating female 1-36 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - biochemical and metabolic Reproductive - Effects on Newborn - physical

REFERENCE :: CPEDAM Clinical Pediatrics (Philadelphia). (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1962- Volume(issue)/page/year: 23,352,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 126 gm/kg

SEX/DURATION :: female 1-18 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: FDTHES Fetal Diagnosis and Therapy (Basel). (S. Karger, Postfach. CH-4009 Basel, Switzerland) V.5- 1990- Volume(issue)/page/year: 9,155,1994

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 2394 mg/kg

SEX/DURATION :: female 1-36 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - Apgar score (human only)

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 219,768,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 2047 mg/kg

SEX/DURATION :: female 27-40 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - physical

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 219,768,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 5320 mg/kg

SEX/DURATION :: female 2-39 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,332,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 5320 mg/kg

SEX/DURATION :: female 2-39 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

REFERENCE :: JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,332,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 5320 mg/kg

SEX/DURATION :: female 2-39 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

REFERENCE :: JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,332,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 600 mg/kg

SEX/DURATION :: female 13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 45,603,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 34 gm/kg

SEX/DURATION :: male 60 day(s) pre-mating female 2 week(s) pre-mating - 1 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2400 mg/kg

SEX/DURATION :: female 7-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

REFERENCE :: NETEEC Neurotoxicology and Teratology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.9- 1987- Volume(issue)/page/year: 13,471,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6 gm/kg

SEX/DURATION :: female 8-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - urogenital system

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 35,28A,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 660 mg/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year: 64,545,1990

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 432 mg/kg

SEX/DURATION :: female 11-13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 1,367,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 432 mg/kg

SEX/DURATION :: female 8-10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 1,367,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 519 mg/kg

SEX/DURATION :: female 8-10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

REFERENCE :: TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 1,367,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 600 mg/kg

SEX/DURATION :: female 9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: AJMGDA American Journal of Medical Genetics. (John Wiley & Sons Ltd., 605 Third Ave., New York, NY 10158) V.1- 1977- Volume(issue)/page/year: 70,303,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 2400 mg/kg

SEX/DURATION :: female 7-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System

REFERENCE :: LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,763,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 600 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 35,29A,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 18 gm/kg

SEX/DURATION :: female 21-50 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 33,45A,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4550 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4550 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1950 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 945 mg/kg

SEX/DURATION :: female 6-8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - urogenital system

REFERENCE :: 36DLAV "Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy, Proceedings of a Symposium, Nottingham, UK, 1975," Legg, N.J., et al., eds., Kent, UK, MCS Consultants, 1976 Volume(issue)/page/year: -,105,1976

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 300 mg/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

REFERENCE :: TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 29(2),47A,1984 *** REVIEWS *** TOXICOLOGY REVIEW JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,333,1980 TOXICOLOGY REVIEW PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979 TOXICOLOGY REVIEW APJUA8 Acta Pharmaceutica Jugoslavica. (FDH, Masarykova 2, 41000 Zagreb, Yugoslavia) V.1-41, 1951-1991. Volume(issue)/page/year: 41,79,1991 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3895 No. of Facilities: 245 (estimated) No. of Industries: 4 No. of Occupations: 6 No. of Employees: 5848 (estimated) No. of Female Employees: 3255 (estimated)

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[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H315-H319-H335-H360

[ 警示性声明 ]:
P201-P280-P301 + P312 + P330-P305 + P351 + P338-P308 + P313

[ 个人防护装备 ]:
Eyeshields;Faceshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ 危害码 (欧洲) ]:
Xn:Harmful

[ 风险声明 (欧洲) ]:
R22;R36/37/38

[ 安全声明 (欧洲) ]:
S26-S45-S36/37-S16

[ 危险品运输编码 ]:
UN 1230 3/PG 2

[ WGK德国 ]:
3

[ RTECS号 ]:
YV7875000

[ 包装等级 ]:
III

[ 危险类别 ]:
8

[ 海关编码 ]:
2915600000

详细合成路线

丙戊酸上游产品

丙戊酸下游产品

1.由二丙基丙二酸经消除脱羧而得。将二丙基丙二酸投入反应锅，加热至180℃，反应物渐渐熔化，逸出大量二氧化碳气体。消除反应结束后，减压蒸馏，收集112-114℃（0.93-1.06kPa）馏分，即为2-丙基戊酸，收率86%。

2.制法：

二丙基丙二酸（3）：于装有搅拌器、回流冷凝器的反应瓶中，加入二丙基丙二酸二乙酯（2）122g（0.5mol），乙醇220mL，4%的氢氧化钾400g，搅拌下回流反应4h。减压蒸出乙醇。冷却至室温，慢慢加入浓盐酸，调至PH1，析出固体。冷却，抽滤，水洗，干燥，得二丙基丙二酸（3）黄色晶体75.0g，收率80%，mp.155～158℃。2-丙基戊酸（1）：于反应瓶中加入二丙基丙二酸（3）75.0g（0.4mol），油浴慢慢加热至180℃，反应物逐渐熔化，并放出大量二氧化碳气体，至无二氧化碳气体逸出为止。减压蒸馏，收集120～123℃/1.86kPa的馏分，得浅黄色2-正丙基物酸^①（1）49.5，收率86%，nD¹⁴1.4252。注：①也可用乙酰乙酸乙酯与正溴丙烷反应后，再进行碱性水解来制备。

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[ 海关编码 ]: 2915900090

[ 中文概述 ]:
2915900090. 其他饱和无环一元羧酸及其酸酐（酰卤、过氧）化物、过氧酸及其卤化、硝化、磺化、亚硝化衍生物. 增值税率:17.0%. 退税率:9.0%. 监管条件:AB(入境货物通关单,出境货物通关单). 最惠国关税:5.5%. 普通关税:30.0%

[ 申报要素 ]: 品名, 成分含量, 用途

[ 监管条件 ]: A.入境货物通关单 B.出境货物通关单

[ 检验检疫 ]: R.进口食品卫生监督检验 S.出口食品卫生监督检验 M.进口商品检验 N.出口商品检验

[ Summary ]:
2915900090 other saturated acyclic monocarboxylic acids and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives VAT:17.0% Tax rebate rate:9.0% Supervision conditions:AB(certificate of inspection for goods inward,certificate of inspection for goods outward) MFN tariff:5.5% General tariff:30.0%

Synergism of arsenic trioxide and MG132 in Raji cells attained by targeting BNIP3, autophagy, and mitochondria with low doses of valproic acid and vincristine.

Eur. J. Cancer 50(18) , 3243-61, (2014)

We previously demonstrated that arsenic trioxide (ATO) and proteasome inhibitor MG132 synergistically induced cell death in promonocytic leukaemia cell line U937 but were antagonistic in Burkitt's lym...

Combined histone deacetylase inhibition and tamoxifen induces apoptosis in tamoxifen-resistant breast cancer models, by reversing Bcl-2 overexpression.

Breast Cancer Res. 17 , 26, (2015)

The emergence of hormone therapy resistance, despite continued expression of the estrogen receptor (ER), is a major challenge to curing breast cancer. Recent clinical studies suggest that epigenetic m...

HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity.

Hum. Mol. Genet. 24 , 3257-71, (2015)

Huntington's disease (HD) is a fatal neurodegenerative disease, caused by expansion of polyglutamine repeats in the Huntingtin gene, with longer expansions leading to earlier ages of onset. The HD iPS...

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公司名：上海化源世纪贸易有限公司

区域：上海市普陀区

价格：

联系人：徐乾明

产品详情：丙戊酸

公司名：上海吉至生化科技有限公司

区域：上海市奉贤区

价格：
￥98.0/25ml ￥248.0/100ml

联系人：刘佳

产品详情：丙戊酸

公司名：上海源溪生物科技有限公司

区域：上海市浦东新区

价格：
￥需询单/1g

联系人：赖经理

产品详情：Valproic acid

公司名：上海脉铂医药科技有限公司

区域：上海市嘉定区

价格：
￥489.0/1g ￥789.0/5g ￥1189.0/10g ￥需询单/1g

联系人：李先生

产品详情：Valproic acid

公司名：上海创赛科技有限公司

区域：上海市嘉定区

价格：
￥71.0/25ml ￥198.0/100ml ￥836.0/500ml ￥需询单/1ml

联系人：夏言

产品详情：[Perfemiker]丙戊酸,99%

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[丙戊酸]-作用-生物活性-丙戊酸活性实验方法

2018-12-31 19:54:30

丙戊酸，英文名Valproic acid，它是支链脂肪酸，其可能增强中枢GABA能神经传递并抑制Na +通道。目前，丙戊酸的各种分子作用机制尚未完全阐明。据报道，丙戊酸在体外是组蛋白脱乙酰酶（HDAC）的有效抑制剂。还注意到丙戊酸可减轻HDAC依赖性转录抑制并导致培养细胞中组蛋白的高度乙酰化。另外...

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