143-67-9

• 常用中文名：硫酸长春碱
• 常用英文名：Vinblastine Sulfate
• CAS号：143-67-9
• 分子式：C₄₆H₆₀N₄O₁₃S
• 分子量：909.053
• 相关类别： 原料药 抗肿瘤药 天然来源类抗肿瘤药
• 发布时间：2018-08-24 12:32:46
• 更新时间：2024-01-02 09:49:34
• Vinblastine sulfate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。

名称

• 中文名: 硫酸长春碱
• 英文名: vincaleukoblastine sulfate
• 中文别名: 硫酸长春花碱
• 英文别名: (3aR,4R,5S,5aR,10bR,13aR)-4-(acétyloxy)-3a-éthyl-9-[(13S,15S,17S)-17-éthyl-17-hydroxy-13-(méthoxycarbonyl)-1,11-diazatétracyclo[13.3.1.0.0]nonadéca-4(12),5,7,9-tétraén-13-yl]-5-hydroxy-8-m; vinbalastine; Velsar; EINECS 205-606-0; Vincaleukoblastine, (2'β)-, sulfate (1:1); VLB; velbe; velban; methyl (3aR,4R,5S,5aR,10bR,13aR)-4-(acetyloxy)-3a-ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0.0]nonadeca-4(12),5,7,9-tetraen-13-yl]-5-hydr; Vinblastine-d3; (2'β)-Vincaleukoblastine sulfate (1:1); (3aR,4R,5S,5aR,10bR,13aR)-4-(acétyloxy)-3a-éthyl-9-[(13S,15S,17S)-17-éthyl-17-hydroxy-13-(méthoxycarbonyl)-1,11-diazatétracyclo[13.3.1.0.0]nonadéca-4(12),5,7,9-tétraén-13-yl]-5-hydroxy-8-méthoxy-6-méthyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate de méthyle sulfate (salt); Periblastine; vincaleukoblastine, (3β,4'β)-, sulfate (1:1); VLB Vincaleukoblastine sulfate salt; éthoxy-6-méthyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate de méthyle sulfate (salt); oxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate sulfate (salt); (+)-vinblastine; Vinblastine (sulfate); Vinblastine sulfate; Vincaleukoblastine sulfate salt; Methyl-(3aR,4R,5S,5aR,10bR,13aR)-4-(acetyloxy)-3a-ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0.0]nonadeca-4(12),5,7,9-tetraen-13-yl]-5-hydr; Methyl-(3aR,4R,5S,5aR,10bR,13aR)-4-(acetyloxy)-3a-ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0.0]nonadeca-4(12),5,7,9-tetraen-13-yl]-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-5-carboxylatsulfat(salt); MFCD00082457; exal; methyl (3aR,4R,5S,5aR,10bR,13aR)-4-(acetyloxy)-3a-ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0.0]nonadeca-4(12),5,7,9-tetraen-13-yl]-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate sulfate (salt); oxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-5-carboxylatsulfat(salt); rozevinsulfate

物化性质

• 密度: 1.37 g/cm3
• 熔点: 267 °C (dec.)(lit.)
• 分子式: C₄₆H₆₀N₄O₁₃S
• 分子量: 909.053
• 精确质量: 908.387756
• PSA: 237.08000
• LogP: 4.35970
• 外观性状: 白色粉末
• 储存条件:

  2-8ºC条件下保存。

• 稳定性:

  常温常压下稳定。

• 水溶解性: >=1 g/100 mL at 24.5 ºC
• 计算化学:

  四、计算化学数据：

  1、 氢键供体数量：5

  2、 氢键受体数量：16

  3、 可旋转化学键数量：10

  4、 拓扑分子极性表面积（TPSA）：229

  5、 重原子数量：64

  6、 表面电荷：0

  7、 复杂度：1780

  8、 同位素原子数量：0

  9、 确定原子立构中心数量：9

  10、 不确定原子立构中心数量：0

  11、 确定化学键立构中心数量：0

  12、 不确定化学键立构中心数量：0

  13、 共价键单元数量：2

• 更多:

  一、物性数据：

  1. 熔点（ºC）：267ºC

  2. 比旋光度（º）： -21.7 º

生物活性

• 描述: Vinblastine sulfate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 >> 自噬 >> 自噬
  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
  天然产物 >> 生物碱
  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.

MSDS

Name: Vinblastine sulfate 96.0-102.0% (hplc) Material Safety Data Sheet Synonym: CAS: 143-67-9 Section 1 - Chemical Product MSDS Name:Vinblastine sulfate 96.0-102.0% (hplc) Material Safety Data Sheet Synonym: Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS CAS# Chemical Name content EINECS# 143-67-9 Vinblastine sulfate 96-102% 205-606-0 Hazard Symbols: T Risk Phrases: 22 37/38 41 61 Section 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW Harmful if swallowed. Irritating to respiratory system and skin. Risk of serious damage to eyes. May cause harm to the unborn child.Harmful.Hygroscopic (absorbs moisture from the air). Potential Health Effects Eye: May cause irreversible eye injury. Skin: Causes skin irritation. Ingestion: Harmful if swallowed. Inhalation: Causes respiratory tract irritation. Chronic: May cause digestive tract disturbances. Section 4 - FIRST AID MEASURES Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid immediately. Skin: Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Get medical aid if irritation develops or persists. Ingestion: Get medical aid immediately. Wash mouth out with 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: 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. Extinguishing Media: Use water spray, dry chemical, or carbon dioxide. 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. Section 7 - HANDLING and STORAGE Handling: Do not breathe dust, vapor, mist, or gas. Do not get in eyes, on skin, or on clothing. Use only in a chemical fume hood. Storage: Store in a tightly closed container. Store in a dry area. Keep refrigerated. (Store below 4C/39F.) Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION Engineering Controls: Use adequate ventilation to keep airborne concentrations low. Exposure Limits CAS# 143-67-9: Personal Protective Equipment Eyes: Not available. Skin: Wear appropriate protective gloves to prevent skin exposure. Clothing: Wear appropriate protective clothing to prevent skin exposure. Respirators: Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced. Section 9 - PHYSICAL AND CHEMICAL PROPERTIES Physical State: Crystalline powder Color: white - slightly yellow Odor: Not available. pH: Not available. Vapor Pressure: Not available. Viscosity: Not available. Boiling Point: Not available. Freezing/Melting Point: 267 deg C Autoignition Temperature: Not available. Flash Point: Not available. Explosion Limits, lower: Not available. Explosion Limits, upper: Not available. Decomposition Temperature: Solubility in water: negligible in water Specific Gravity/Density: Molecular Formula: Molecular Weight: 909.05 Section 10 - STABILITY AND REACTIVITY Chemical Stability: Not available. Conditions to Avoid: Incompatible materials, light, exposure to moist air or water. Incompatibilities with Other Materials: Strong oxidizing agents. Hazardous Decomposition Products: Carbon monoxide, oxides of nitrogen, oxides of sulfur, carbon dioxide. Hazardous Polymerization: Has not been reported Section 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 143-67-9: YY8400000 LD50/LC50: CAS# 143-67-9: Oral, mouse: LD50 = 423 mg/kg; Oral, rat: LD50 = 305 mg/kg. Carcinogenicity: Vinblastine sulfate - Not listed by ACGIH, IARC, or NTP. Other: See actual entry in RTECS for complete information. Section 12 - ECOLOGICAL INFORMATION Section 13 - DISPOSAL CONSIDERATIONS Dispose of in a manner consistent with federal, state, and local regulations. 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. Section 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives Hazard Symbols: T Risk Phrases: R 61 May cause harm to the unborn child. R 22 Harmful if swallowed. R 37/38 Irritating to respiratory system and skin. R 41 Risk of serious damage to eyes. Safety Phrases: S 53 Avoid exposure - obtain special instructions before use. S 26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S 37/39 Wear suitable gloves and eye/face protection. 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# 143-67-9: No information available. Canada None of the chemicals in this product are listed on the DSL/NDSL list. CAS# 143-67-9 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 143-67-9 is not listed on the TSCA inventory. It is for research and development use only. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

毒理学数据: 二、毒理学数据： 1、急性毒性：大鼠经口LD50：305 mg/kg； 大鼠腹腔LD50：1 mg/kg； 大鼠皮下LD50：355 mg/kg； 大鼠静脉LD50：37 mg/kg； 小鼠经口LD50：423 mg/kg； 小鼠腹腔LD50：2700 ug/kg； 小鼠皮下LD50：324 mg/kg。 生态学数据: 三、生态学数据： 其它有害作用：该物质对环境可能有危害，对水体应给予特别注意。 CHEMICAL IDENTIFICATION RTECS NUMBER : YY8400000 CAS REGISTRY NUMBER : 143-67-9 LAST UPDATED : 199806 DATA ITEMS CITED : 52 MOLECULAR FORMULA : C46-H58-N4-O9.H2-O4-S MOLECULAR WEIGHT : 909.16 WISWESSER LINE NOTATION : T C6 B5665/BS 2AB S BX IN QN NU&&TTTJ FO1 I1 KVO1 KQ LOV1 M2 E- CT F6 D596 A EN ON&&TTJ CVO1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human DOSE/DURATION : 557 ug/kg TOXIC EFFECTS : Blood - leukopenia Skin and Appendages - hair TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 305 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 - rat DOSE/DURATION : 1 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 355 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 : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 37 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 : 423 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 : 2700 ug/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 : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 324 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 : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 9500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 500 ug/kg TOXIC EFFECTS : Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 4300 ug/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 : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3 mg/kg/15D-I TOXIC EFFECTS : Gastrointestinal - other changes Blood - leukopenia Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 500 ug/kg/5D-I TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from stomach Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 125 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 - body wall TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular DOSE : 125 ug/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 350 ug/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 250 ug/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 50 ug/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) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 350 ug/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 10 mg/kg SEX/DURATION : female 11-14 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 500 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 1 mg/kg SEX/DURATION : female 1 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - other effects to embryo TYPE OF TEST : Sex chromosome loss and nondisjunction TYPE OF TEST : Cytogenetic analysis TYPE OF TEST : Micronucleus test TYPE OF TEST : DNA inhibition TYPE OF TEST : Sperm Morphology TYPE OF TEST : Micronucleus test TYPE OF TEST : Mutation test systems - not otherwise specified TYPE OF TEST : Mutation test systems - not otherwise specified TYPE OF TEST : Sex chromosome loss and nondisjunction TYPE OF TEST : Sperm Morphology MUTATION DATA TEST SYSTEM : Rodent - hamster DOSE/DURATION : 24 ug/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 327,237,1995 *** REVIEWS *** IARC Cancer Review:Animal Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,349,1981 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,349,1981 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,371,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 83934 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 1386 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 83934 No. of Facilities: 273 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 14022 (estimated) No. of Female Employees: 10067 (estimated)

安全

• 符号: GHS05, GHS07
• 信号词: Danger
• 危害声明: H302-H315-H318-H335
• 警示性声明: P280-P301 + P312 + P330-P305 + P351 + P338 + P310
• 危害码 (欧洲): T:Toxic
• 风险声明 (欧洲): R22;R36/37/38;R41;R61
• 安全声明 (欧洲): 26-36/39-53-45-37/39-36/37/39
• 危险品运输编码: 1544
• WGK德国: 3
• RTECS号: YY8400000
• 包装等级: II
• 危险类别: 6.1(a)
• 海关编码: 2942000000

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