865-21-4

• 常用中文名：长春质碱
• 常用英文名：Vinblastine
• CAS号：865-21-4
• 分子式：C₄₆H₅₈N₄O₉
• 分子量：810.974
• 相关类别： 生物化工 植物提取物
• 发布时间：2018-03-26 08:00:00
• 更新时间：2024-01-03 06:31:43
• Vinblastine是一种针对各种癌症类型的有细胞毒性的生物碱。 长春花碱可抑制微管的形成,抑制nAChR的IC50值为8.9 μM。
• 抗肿瘤作用长春花碱 具有抗肿瘤作用，主要用于何杰金氏病、绒毛膜癌（对氨甲蝶呤已产生抗药者，则需用较大剂量)；此外，对淋巴肉瘤、蕈样霉菌病（Mycosis fungoides）、白血病、横纹肌软骨瘤、黑色素瘤、精母细胞瘤、畸胎瘤、星形细胞瘤、肉织细胞肉瘤、癌（胸、肺、口腔、胃、结肠、直肠、卵巢、颈部、子宫、膀胱、肾等部位）等的抗肿瘤作用还需进一步肯定。疗效出现较快，用药后3d内肿瘤明显缩小或发热消退，但缓解期较短，有的在用维持量或停药后2～3周又趋复发。对实验性肿瘤的作用如下：对DBA/2小鼠的移植性淋巴细胞白血病P-1534有显著治疗效果，可以延长小鼠的生存时间，但很少获“治愈”。对DBA/1小鼠乳房肿瘤有明显抑制
  长春花碱 作用。
  在临床上对乳腺癌有一定的治疗效果。长春花碱 对小鼠白血病L1210、小鼠移植性淋巴细胞白血病P-1534、AKP-白血病、大鼠W258、IRC741/1398白血病、小鼠肉瘤S180、艾氏腹水癌和移植性及自发性乳腺癌都有实验治疗作用，并可防止AKP小鼠的自发性白血病，能使患IRC741白血病的Fisher大鼠血流中存在的瘤细胞迅速消失。长春花碱 的作用机制与秋水仙碱相似，能抑制肿瘤细胞如艾氏腹水癌、腹水癌L1210和人 的单核细胞性白血病以及正常动物骨髓细胞的有丝分裂，使停止于中期。长春花碱 能干扰微管蛋白的合成，从而阻止微管蛋白装配成有功能的纺锤丝。与秋水仙碱不同之处为该抑制作用较强，且可被谷氨酸和色氨酸所对抗。早期的体外实验未能证明长春花碱 于治疗浓度下对DNA和RNA的合成有明显影响，但后来的体内实验发现艾氏腹水癌小鼠给长春花碱 （2mg/kg）一剂，即能减少3H-尿嘧啶核苷掺入癌细胞的RNA。体外实验如果药物与艾氏腹水癌细胞一起较长时间（1h）温育后，3H-尿嘧啶核苷掺入RNA亦显著被抑制，于2×10-4M 即产生明显抑制，且被大剂量谷氨酸所对抗。对大鼠瓦克肉瘤，长春花碱 能明显抑制3H-胸腺嘧啶脱氧核苷掺入DNA，对瘤细胞核仁的DNA合成的抑制作用比非核仁的DNA要强。近有报道长春花碱 能抑制艾氏腹水癌细胞的DNA依赖性RNA聚合酶。
  体内过程
  在人，0.2mg/kg静注，血清峰浓度低于0.05mg/ml。大鼠静注氘标记长春花碱 后30min血液中放射活性不到注入量的1.5%，由于24h内仅有6.6%经肾排出，其在体内消除迅速似并非由于经肾排泄的关系。胆道排泄可能是长春花碱 清除的主要途径，氚标记长春花碱 如给大鼠腹腔注射，于给药后1～2h达血浆峰浓度。

名称

• 中文名: 长春质碱
• 英文名: vincaleukoblastine
• 中文别名: 长春花碱; 长春碱
• 英文别名: UNII-5V9KLZ54CY; vinblastine sulfuric acid salt; Vincoblastine; (3aR-(3aα,4β,5β,5aβ,9(3R*,5S*,7R*,9S*),10bR*,13aα))-methyl 4-(acetyloxy)-3a-ethyl-9-(5-ethyl-1,4,5,6,7,8,9,10-octahydro-5-hydroxy-9-(methoxycarbonyl)-2H-3,7-methanoazacycloundecino(5,4-b)indol-9-yl)-3a,4,5,5a,6,11,12,13a-octahydro-5-hydroxy-8-methoxy-6-methyl-1H-indolizino(8,1-cd)carbazole-5-carboxylate; Vinblastine; Vincaleucoblastin; 1H-Indolizino(8,1-cd)carbazole-5-carboxylic acid, 4-(acetyloxy)-3a-ethyl-9-(5-ethyl-1,4,5,6,7,8,9,10-octahydro-5-hydroxy-9-(methoxycarbonyl)-2H-3,7-methanoazacycloundecino(5,4-b)indol-9-yl)-3a,4,5,5a,6,11,12,13a-octahydro-5-hydroxy-8-methoxy-6-methyl-, methyl ester, (3aR-(3aα,4β,5β,5aβ,9(3R*,5S*,7R*,9S*),10bR*,13aα))-; Vincaleukoblastine; Vinblastine,Vincaleukoblastine; Rozevin; Vincaleucoblastine; Vinblastine sulphate; EINECS 212-734-0

物化性质

• 密度: 1.4±0.1 g/cm3
• 熔点: 211 - 216ºC
• 分子式: C₄₆H₅₈N₄O₉
• 分子量: 810.974
• 精确质量: 810.420349
• PSA: 154.10000
• LogP: 4.18
• 折射率: 1.671
• 储存条件: -20C

生物活性

• 描述: Vinblastine是一种针对各种癌症类型的有细胞毒性的生物碱。 长春花碱可抑制微管的形成,抑制nAChR的IC50值为8.9 μM。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> 微管/微管蛋白
  信号通路 >> 细胞骨架 >> 微管/微管蛋白
  信号通路 >> 跨膜转运 >> 胆碱受体
  信号通路 >> 神经信号通路 >> 胆碱受体
  研究领域 >> 癌症
• 靶点:

  IC50: 8.9 μM(nAChR)[1]

• 体外研究: 长春碱不会使纺锤体微管解聚,但它有效阻断有丝分裂(例如,HeLa细胞中IC50为0.8 nM),细胞死于细胞凋亡[2]。在NB4细胞中,长春碱产生p53和DNA片段化的改变。长春碱治疗通过诱导细胞凋亡产生Bax/Bcl-2失衡具有抗增殖作用。长春碱处理抑制NFκB表达并抑制NFκB-DNA结合活性,同时维持JNK活化,随后通过半胱天冬酶依赖性途径导致细胞凋亡反应[3]。发现长春碱诱导细胞凋亡,如线粒体膜电位的丧失,细胞色素c和细胞凋亡诱导因子的释放,caspase-9和3的激活以及Poly(ADP-核糖)聚合酶的裂解所证明[4]。
• 体内研究: 长春碱是一种广泛使用的抗癌药物,具有不良副作用。它与载体分子的结合可能是减少这些副作用的有效策略[5]。
• 参考文献:

  [1]. McKay DB, et al. Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. Proc Soc Exp Biol Med. 1993 Jul;203(3):372-6.

  [2]. Pandya P, et al. Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets. J Mol Graph Model. 2014 Nov;54:1-9.

  [3]. Calviño E, et al. JNK and NFκB dependence of apoptosis induced by vinblastine in human acute promyelocytic leukaemia cells. Cell Biochem Funct. 2015 Jun;33(4):211-9.

  [4]. Selimovic D, et al. Vinblastine-induced apoptosis of melanoma cells is mediated by Ras homologous A protein (Rho A) via mitochondrial and non-mitochondrial-dependent mechanisms. Apoptosis. 2013 Aug;18(8):980-97.

  [5]. Bánóczi Z, et al. Synthesis and in vitro antitumor effect of vinblastine derivative-oligoarginine conjugates. Bioconjug Chem. 2010 Nov 17;21(11):1948-55.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : YY8050000 CHEMICAL NAME : Vincaleukoblastine CAS REGISTRY NUMBER : 865-21-4 LAST UPDATED : 199612 DATA ITEMS CITED : 44 MOLECULAR FORMULA : C46-H58-N4-O9 MOLECULAR WEIGHT : 811.08 WISWESSER LINE NOTATION : T C6 B5665 2AB S BX IN QN NU JH&&TTTTJ FO1 I KVO1 KQ LOV1 M2 E- NT F6 E596 A BN LM&&TTJ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - man DOSE/DURATION : 2319 ug/kg/38W-I TOXIC EFFECTS : Cardiac - cardiomyopathy including infarction TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Ocular SPECIES OBSERVED : Human DOSE/DURATION : 14 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - visual field changes Sense Organs and Special Senses (Eye) - conjunctive irritation Sense Organs and Special Senses (Eye) - effect, not otherwise specified TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - man DOSE/DURATION : 80 ug/kg TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2 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 : 3120 ug/kg TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) Immunological Including Allergic - decreased immune response TYPE OF TEST : LD10 - Lethal Dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 20 mg/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 : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5120 ug/kg/4W-I TOXIC EFFECTS : Endocrine - other changes Blood - changes in leukocyte (WBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2 mg/kg/7W-I TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Endocrine - tumors Skin and Appendages - tumors TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 7 mg/kg/26W-I TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Kidney, Ureter, Bladder - tumors TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 62500 ug/kg SEX/DURATION : female 10-11 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - behavioral TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 7 mg/kg SEX/DURATION : male 1 day(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 : Intravenous DOSE : 500 ug/kg SEX/DURATION : female 1 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 300 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 7500 ug/kg SEX/DURATION : female 4-28 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 100 ug/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : Specific locus test TYPE OF TEST : Heritable translocation test TYPE OF TEST : Micronucleus test TYPE OF TEST : Cytogenetic analysis TYPE OF TEST : Sex chromosome loss and nondisjunction TYPE OF TEST : Dominant lethal test TYPE OF TEST : Sperm Morphology MUTATION DATA TYPE OF TEST : Sex chromosome loss and nondisjunction TEST SYSTEM : Rodent - hamster Lung DOSE/DURATION : 5 ug/L REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 287,29,1993 *** REVIEWS *** TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 TOXICOLOGY REVIEW ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI. Volume(issue)/page/year: 5,447,1965 TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 2,159,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3898 No. of Facilities: 161 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 2136 (estimated) No. of Female Employees: 1159 (estimated)

安全

• 危险品运输编码: UN 1544
• 包装等级: II
• 危险类别: 6.1(a)