26305-03-3

• 常用中文名：胃蛋白酶抑制剂
• 常用英文名：Pepstatin
• CAS号：26305-03-3
• 分子式：C₃₄H₆₃N₅O₉
• 分子量：685.892
• 相关类别： 生物化工 酶及辅酶类药
• 发布时间：2018-07-08 21:35:36
• 更新时间：2024-01-03 12:08:34
• Pepstatin 是由放线菌类产生的一种特异性的天冬氨酸蛋白酶 (aspartic proteases) 抑制剂,能够抑制 hemoglobin-pepsin,hemoglobin-proctase,casein-pepsin,casein-proctase,casein-acid protease 和 hemoglobin-acid protease 的活性,IC50 值分别为 4.5 nM,6.2 nM,150 nM,290 nM,520 nM 和 260 nM；同时可抑制 HIV protease 的活性。

名称

• 中文名: 胃酶抑素 A
• 英文名: Pepstatin A
• 中文别名: 胃蛋白酶抑制剂; 抑肽素
• 英文别名: N-Isovaleryl-L-valyl-L-valyl-3-hydroxy-6-methyl-γ-aminoheptanoyl-L-alanyl-3-hydroxy-6-methyl-γ-aminoheptanoic acid; N-(3-Methylbutanoyl)-L-valyl-N-[(3S,4S)-1-{[(2S)-1-{[(2S,3S)-1-carboxy-2-hydroxy-5-methyl-3-hexanyl]amino}-1-oxo-2-propanyl]amino}-3-hydroxy-6-methyl-1-oxo-4-heptanyl]-L-valinamide; Pepstatin A; Pepstatin (USAN); L-Valinamide, N-(3-methyl-1-oxobutyl)-L-valyl-N-[(1S,2S)-4-[[(1S)-2-[[(1S)-1-[(1S)-2-carboxy-1-hydroxyethyl]-3-methylbutyl]amino]-1-methyl-2-oxoethyl]amino]-2-hydroxy-1-(2-methylpropyl)-4-oxobutyl]-; pepsininhibitors735a; IHN; peptistatin A; EINECS 247-600-0; Procidin S 735A; procidins735a; PEPSTATIN; ahpatininc; ahpatinin C; pepstatine A; Iva-Val-Val-Sta-Ala-Sta-OH; PepstainA; IVA-VAL-VAL-STA-ALA-STA; N-(3-Methylbutanoyl)-L-valyl-N-[(3S,4S)-1-{[(2S)-1-{[(2S,3S)-1-carboxy-2-hydroxy-5-methylhexan-3-yl]amino}-1-oxopropan-2-yl]amino}-3-hydroxy-6-methyl-1-oxoheptan-4-yl]-L-valinamide; MFCD00060740; N-Isovaleryl-L-valyl-L-valyl-3-hydroxy-6-methyl-g-aminoheptanoyl-L-alanyl-3-hydroxy-6-methyl-g-aminoheptanoic Acid; PEPSTATIN A SYNTHETIC; Isovalerylpepstatin; N-(3-Methyl-1-oxobutyl)-L-valyl-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoyl-N-((1S)-1-((1S)-2-carboxy-1-hydroxyethyl)-3-methylbutyl)-L-alaninamide

物化性质

• 密度: 1.1±0.1 g/cm3
• 沸点: 997.6±65.0 °C at 760 mmHg
• 熔点: 233 °C (dec.)(lit.)
• 分子式: C₃₄H₆₃N₅O₉
• 分子量: 685.892
• 闪点: 557.1±34.3 °C
• 精确质量: 685.462585
• PSA: 223.26000
• LogP: 2.16
• 外观性状: 固体
• 蒸汽压: 0.0±0.6 mmHg at 25°C
• 折射率: 1.504
• 储存条件:

  2-8℃

• 稳定性:

  常温常压下稳定

  避免接触氧化剂
• 水溶解性: 10% acetic acid in methanol: 1 mg/mL
• 分子结构:

  1、 摩尔折射率：181.82

  2、 摩尔体积（m³/mol）：613.6

  3、 等张比容（90.2K）：1573.8

  4、 表面张力（dyne/cm）：43.2

  5、 极化率（10 ^-24cm ³）：72.08

• 计算化学:

  1、 疏水参数计算参考值（XlogP）：3

  2、 氢键供体数量：8

  3、 氢键受体数量：9

  4、 可旋转化学键数量：22

  5、 互变异构体数量：32

  6、 拓扑分子极性表面积（TPSA）：223

  7、 重原子数量：48

  8、 表面电荷：0

  9、 复杂度：1060

  10、 同位素原子数量：0

  11、 确定原子立构中心数量：7

  12、 不确定原子立构中心数量：0

  13、 确定化学键立构中心数量：0

  14、 不确定化学键立构中心数量：0

  15、 共价键单元数量：1

• 更多:

  1. 性状： 未确定

  2. 密度（g/mL,25/4℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：233

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC,5.2kPa）：未确定

  7. 折射率：未确定

  8. 闪点（ºC）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：溶于甲醇

生物活性

• 描述: Pepstatin 是由放线菌类产生的一种特异性的天冬氨酸蛋白酶 (aspartic proteases) 抑制剂,能够抑制 hemoglobin-pepsin,hemoglobin-proctase,casein-pepsin,casein-proctase,casein-acid protease 和 hemoglobin-acid protease 的活性,IC50 值分别为 4.5 nM,6.2 nM,150 nM,290 nM,520 nM 和 260 nM；同时可抑制 HIV protease 的活性。
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> HIV蛋白酶
  信号通路 >> 代谢酶/蛋白酶 >> 蛋白酶体
  研究领域 >> 感染
  天然产物 >> 其他
  多肽产品
• 靶点:

  IC50: 4.5 nM (Hemoglobin-pepsin), 6.2 nM (Hemoglobin-proctase), 150 nM (Casein-pepsin), 260 nM (Hemoglobin-acid protease), 290 nM (Casein-proctase), 520 nM (Casein-acid protease)[1]

• 体外研究: Pepstatin是一种由放线菌产生的特异性酸性蛋白酶抑制剂,血红蛋白-胃蛋白酶,血红蛋白-直链酶,酪蛋白-胃蛋白酶,酪蛋白-酪蛋白酶,酪蛋白-的IC50分别为4.5 nM,6.2 nM,150 nM,290 nM,520 nM和260 nM酸性蛋白酶和血红蛋白酸性蛋白酶分别[1]。胃蛋白酶抑制素(Pepstatin A)抑制重组HIV蛋白酶,IC50为250μM。 Pepstatin对细胞蛋白质合成没有影响,可能不会发挥严重的细胞毒性[2]。
• 体内研究: 胃蛋白酶抑制剂具有非常低的毒性,通过ip途径对小鼠,大鼠,兔和狗的LD50为1090mg/kg,875mg/kg,820mg/kg和450mg/kg,并且对所有人均为> 2000mg/kg。物种通过口服途径。胃蛋白酶抑制剂(0.5-50 mg/kg,po)抑制结扎Shay大鼠的幽门胃溃疡[1]。
• 细胞实验: 胃蛋白酶抑制剂A以7mM新鲜溶解于DMSO中。将其非常缓慢地（1：100）稀释到HIV感染的H9悬浮培养基的培养基中，使得没有胃蛋白酶抑制剂A沉淀（最终浓度，70μM胃蛋白酶抑制剂A和1％DMSO），并且培养物在不改变培养基的情况下孵育。持续48小时。作为对照，未感染的H9细胞也与胃酶抑素一起孵育，此外HIV感染和未感染的细胞与1％DMSO孵育但不含胃蛋白酶抑制剂[2]。
• 参考文献:

  [1]. Umezawa H, et al. Pepstatin, a new pepsin inhibitor produced by Actinomycetes. J Antibiot (Tokyo). 1970 May;23(5):259-62.

  [2]. Seelmeier S, et al. Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6612-6.

MSDS

SECTION 1: Identification of the substance/mixture and of the company/undertaking Product identifiers Product name: Pepstatin A REACH No.: A registration number is not available for this substance as the substance or its uses are exempted from registration, the annual tonnage does not require a registration or the registration is envisaged for a later registration deadline. CAS-No.: 26305-03-3 Relevant identified uses of the substance or mixture and uses advised against Identified uses: Laboratory chemicals, Manufacture of substances SECTION 2: Hazards identification Classification of the substance or mixture Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008. This substance is not classified as dangerous according to Directive 67/548/EEC. Label elements The product does not need to be labelled in accordance with EC directives or respective national laws. Other hazards - none SECTION 3: Composition/information on ingredients Substances Formula: C34H63N5O9 C34H63N5O9 Molecular Weight: 685,89 g/mol CAS-No.: 26305-03-3 EC-No.: 247-600-0 No components need to be disclosed according to the applicable regulations. SECTION 4: First aid measures Description of first aid measures General advice Consult a physician. Show this safety data sheet to the doctor in attendance. If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician. In case of skin contact Wash off with soap and plenty of water. Consult a physician. In case of eye contact Flush eyes with water as a precaution. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician. Most important symptoms and effects, both acute and delayed The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in section 11 Indication of any immediate medical attention and special treatment needed no data available SECTION 5: Firefighting measures Extinguishing media Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special hazards arising from the substance or mixture Carbon oxides, nitrogen oxides (NOx) Advice for firefighters Wear self contained breathing apparatus for fire fighting if necessary. Further information no data available SECTION 6: Accidental release measures Personal precautions, protective equipment and emergency procedures Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Avoid breathing dust. For personal protection see section 8. Environmental precautions Do not let product enter drains. Methods and materials for containment and cleaning up Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. Reference to other sections For disposal see section 13. SECTION 7: Handling and storage Precautions for safe handling Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. For precautions see section 2.2. Conditions for safe storage, including any incompatibilities Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C Specific end use(s) Apart from the uses mentioned in section 1.2 no other specific uses are stipulated SECTION 8: Exposure controls/personal protection Control parameters Components with workplace control parameters Exposure controls Appropriate engineering controls Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. Personal protective equipment Eye/face protection Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Body Protection Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Respiratory protection Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). Control of environmental exposure Do not let product enter drains. SECTION 9: Physical and chemical properties Information on basic physical and chemical properties a) AppearanceForm: solid b) Odourno data available c) Odour Thresholdno data available d) pHno data available e) Melting point/freezingMelting point/range: 233 °C point f) Initial boiling point and no data available boiling range g) Flash pointno data available h) Evapouration rateno data available i) Flammability (solid, gas) no data available j) Upper/lowerno data available flammability or explosive limits k) Vapour pressureno data available l) Vapour densityno data available m) Relative densityno data available n) Water solubilityno data available o) Partition coefficient: n- no data available octanol/water p) Auto-ignitionno data available temperature q) Decompositionno data available temperature r) Viscosityno data available s) Explosive propertiesno data available t) Oxidizing propertiesno data available Other safety information no data available SECTION 10: Stability and reactivity Reactivity no data available Chemical stability Stable under recommended storage conditions. Possibility of hazardous reactions no data available Conditions to avoid no data available Incompatible materials Strong acids, Strong bases Hazardous decomposition products Other decomposition products - no data available In the event of fire: see section 5 SECTION 11: Toxicological information Information on toxicological effects Acute toxicity LD50 Oral - rat - > 2.000 mg/kg Skin corrosion/irritation no data available Serious eye damage/eye irritation no data available Respiratory or skin sensitisation no data available Germ cell mutagenicity no data available Carcinogenicity IARC:No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC. Reproductive toxicity no data available Specific target organ toxicity - single exposure no data available Specific target organ toxicity - repeated exposure no data available Aspiration hazard no data available Additional Information RTECS: SC6155000 To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. SECTION 12: Ecological information Toxicity no data available Persistence and degradability no data available Bioaccumulative potential no data available Mobility in soil no data available Results of PBT and vPvB assessment PBT/vPvB assessment not available as chemical safety assessment not required/not conducted Other adverse effects no data available SECTION 13: Disposal considerations Waste treatment methods Product Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging Dispose of as unused product. SECTION 14: Transport information UN number ADR/RID: -IMDG: -IATA: - UN proper shipping name ADR/RID: Not dangerous goods IMDG: Not dangerous goods IATA:Not dangerous goods Transport hazard class(es) ADR/RID: -IMDG: -IATA: - Packaging group ADR/RID: -IMDG: -IATA: - Environmental hazards ADR/RID: noIMDG Marine pollutant: noIATA: no Special precautions for user no data available SECTION 15 - REGULATORY INFORMATION N/A SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

毒理学数据: 急性毒性：大鼠LD50：>2 mg/kg；大鼠腹腔LD50：875mg/kg；小鼠腹腔LD50：1090mg/kg； CHEMICAL IDENTIFICATION RTECS NUMBER : SC6155000 CHEMICAL NAME : Pepstatin A CAS REGISTRY NUMBER : 26305-03-3 LAST UPDATED : 199612 DATA ITEMS CITED : 8 MOLECULAR FORMULA : C34-H63-N5-O9 MOLECULAR WEIGHT : 686.02 WISWESSER LINE NOTATION : QV1YQY1Y1&1&MVY1&MV1YQY1Y1&1&MVYY1&1&MVYY1&1&MV1Y1&1 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 : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PPTCBY Proceedings of the International Symposium of the Princess Takamatsu Cancer Research Fund. (Japan Scientific Soc. Press, 6-2-10 Hongo, Bunkyo-ku, Tokyo 113, Japan) 1st- 1971- Volume(issue)/page/year: 6,57,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 875 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 23,259,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PPTCBY Proceedings of the International Symposium of the Princess Takamatsu Cancer Research Fund. (Japan Scientific Soc. Press, 6-2-10 Hongo, Bunkyo-ku, Tokyo 113, Japan) 1st- 1971- Volume(issue)/page/year: 6,57,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1090 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 23,259,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 23,259,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 450 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 23,259,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 23,259,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 820 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 23,259,1970

安全

• 个人防护装备: Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
• 安全声明 (欧洲): S22-S24/25
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 2
• RTECS号: SC6155000