sodium novobiocin | 1476-53-5

• 物质功能分类: 原料药 - 抗生素类药物 - 其它抗生素类药
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: sodium novobiocin
• 英文别名: novobiocin sodium salt；novobiocin sodium；novobiocin monosodium salt；novobiocin；Albamycin；sodium;4-[[7-[(2R,3R,4S,5R)-4-carbamoyloxy-3-hydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxy-4-hydroxy-8-methyl-2-oxochromen-3-yl]carbamoyl]-2-(3-methylbut-2-enyl)phenolate
• CAS: 1476-53-5
• 化学式: C₃₁H₃₅N₂O₁₁*Na
• 分子量: 634.615
• InChiKey: WWPRGAYLRGSOSU-RNROJPEYSA-M

物化性质

• 熔点：
  215-220 C
• 比旋光度：
  D24 -38° (c = 2.5 in 95% ethanol); D24 -33° (c = 2.5 in water)
• 溶解度：
  H2O中可溶50mg/mL
• 碰撞截面：
  262.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：
  如果遵照规格使用和储存，则不会分解，未有已知危险反应。应避免与氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  -0.0
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  199
• 氢给体数：
  4
• 氢受体数：
  11

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36,S36/37,S37/39
• 危险类别码：
  R43
• WGK Germany：
  2
• 海关编码：
  2941 90 00
• RTECS号：
  RD5425000
• 储存条件：
  密封，在2°C至-8°C下保存

SDS

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Section 1. Chemical Product and Company Identification
Novobiocin Sodium Catalog
N1365, N1149
Common Name/
Number(s).
Trade Name
CAS# 1476-53-5
Manufacturer
RTECS RD5425000
SPECTRUM CHEMICAL MFG. CORP.
TSCA TSCA 8(b) inventory: No
products were found.
Commercial Name(s) Not available.
CI# Not available.
Synonym Not available.
IN CASE OF EMERGENCY
Not available.
Chemical Name
Chemical Family Not available. CALL [phone]
C31H35N2NaO11
Chemical Formula
SPECTRUM CHEMICAL MFG. CORP.

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Section 2.Composition and Information on Ingredients
Exposure Limits
TWA (mg/m3) STEL (mg/m3) CEIL (mg/m3)
Name CAS # % by Weight
1) Novobiocin Sodium 1476-53-5 100
Toxicological Data Novobiocin Sodium:
on Ingredients ORAL (LD50): Acute: 3500 mg/kg [Rat]. 962 mg/kg [Mouse].

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Section 3. Hazards Identification
Potential Acute Health Effects Hazardous in case of skin contact (irritant), of eye contact (irritant), of ingestion, of inhalation (lung irritant).
Potential Chronic Health CARCINOGENIC EFFECTS: Not available.
MUTAGENIC EFFECTS: Not available.
Effects
TERATOGENIC EFFECTS: Not available.
DEVELOPMENTAL TOXICITY: Not available.
Repeated or prolonged exposure is not known to aggravate medical condition.
Novobiocin Sodium

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Section 4. First Aid Measures
Eye Contact Check for and remove any contact lenses. Immediately flush eyes with running water for at least 15 minutes,
keeping eyelids open. Cold water may be used. Do not use an eye ointment. Seek medical attention.
Skin Contact After contact with skin, wash immediately with plenty of water. Gently and thoroughly wash the contaminated skin
with running water and non-abrasive soap. Be particularly careful to clean folds, crevices, creases and groin.
Cold water may be used. Cover the irritated skin with an emollient. If irritation persists, seek medical attention.
Wash contaminated clothing before reusing.
Serious Skin Contact Wash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek immediate
medical attention.
Inhalation Allow the victim to rest in a well ventilated area. Seek immediate medical attention.
Serious Inhalation Not available.
Ingestion Do not induce vomiting. Examine the lips and mouth to ascertain whether the tissues are damaged, a possible
indication that the toxic material was ingested; the absence of such signs, however, is not conclusive. Loosen
tight clothing such as a collar, tie, belt or waistband. If the victim is not breathing, perform mouth-to-mouth
resuscitation. Seek immediate medical attention.
Serious Ingestion Not available.

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Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Flash Points Not available.
Flammable Limits Not available.
Products of Combustion These products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...). Some metallic oxides.
Fire Hazards in Presence of Not available.
Various Substances
Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available.
of Various Substances Risks of explosion of the product in presence of static discharge: Not available.
Fire Fighting Media SMALL FIRE: Use DRY chemical powder.
and Instructions LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
Special Remarks on Not available.
Fire Hazards
Special Remarks on Explosion Not available.
Hazards

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Section 6. Accidental Release Measures
Small Spill Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by
spreading water on the contaminated surface and dispose of according to local and regional authority
requirements.
Large Spill Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water
on the contaminated surface and allow to evacuate through the sanitary system.
Novobiocin Sodium

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Section 7. Handling and Storage
Precautions Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the
residue under a fume hood. Ground all equipment containing material. Do not ingest. Do not breathe dust.
Wear suitable protective clothing In case of insufficient ventilation, wear suitable respiratory equipment If
ingested, seek medical advice immediately and show the container or the label. Avoid contact with skin and eyes
Storage Keep container dry. Keep in a cool place. Ground all equipment containing material. Keep container tightly
closed. Keep in a cool, well-ventilated place. Combustible materials should be stored away from extreme heat
and away from strong oxidizing agents.

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Section 8. Exposure Controls/Personal Protection
Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below
recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to
airborne contaminants below the exposure limit.
Personal Protection Splash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent.
Gloves.
Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used
a Large Spill to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist
BEFORE handling this product.
Exposure Limits Not available.

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Section 9. Physical and Chemical Properties
Physical state and appearance Solid. Odor Not available.
Taste Not available.
634.62 g/mole
Molecular Weight
Color Not available.
pH (1% soln/water) Not available.
Boiling Point Not available.
Melting Point Decomposes.
Critical Temperature Not available.
Specific Gravity Not available.
Not applicable.
Vapor Pressure
Vapor Density Not available.
Volatility Not available.
Odor Threshold Not available.
Water/Oil Dist. Coeff. Not available.
Not available.
Ionicity (in Water)
Dispersion Properties See solubility in water.
Partially soluble in cold water.
Solubility

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Section 10. Stability and Reactivity Data
The product is stable.
Stability
Instability Temperature Not available.
Not available.
Conditions of Instability
Incompatibility with various Not available.
substances
Novobiocin Sodium
Corrosivity Non-corrosive in presence of glass.
Special Remarks on Not available.
Reactivity
Special Remarks on Not available.
Corrosivity
Polymerization No.

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Section 11. Toxicological Information
Routes of Entry Eye contact. Inhalation. Ingestion.
Toxicity to Animals Acute oral toxicity (LD50): 962 mg/kg [Mouse].
Chronic Effects on Humans Not available.
Other Toxic Effects on Hazardous in case of skin contact (irritant), of ingestion, of inhalation (lung irritant).
Humans
Special Remarks on Not available.
Toxicity to Animals
Special Remarks on Not available.
Chronic Effects on Humans
Special Remarks on other Not available.
Toxic Effects on Humans

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Section 12. Ecological Information
Ecotoxicity Not available.
BOD5 and COD Not available.
Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
Toxicity of the Products The products of degradation are more toxic.
of Biodegradation
Special Remarks on the Not available.
Products of Biodegradation

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Section 13. Disposal Considerations
Waste Disposal

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Section 14. Transport Information
DOT Classification Not a DOT controlled material (United States).
Identification Not applicable.
Special Provisions for Not applicable.
Transport
Novobiocin Sodium
DOT (Pictograms)

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Section 15. Other Regulatory Information and Pictograms
No products were found.
Federal and State
Regulations
California
Proposition 65
Warnings
Other Regulations EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances.
WHMIS (Canada) Not controlled under WHMIS (Canada).
Other Classifications
DSCL (EEC) R36/37/38- Irritating to eyes,
respiratory system and skin.
Health Hazard
HMIS (U.S.A.) 2 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
2 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
TDG (Canada)
(Pictograms)
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or
equivalent.
Novobiocin Sodium

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

药理作用及应用

新生霉素钠是新生霉素的钠盐，其抗菌谱与青霉素相似，主要用于耐药性金黄色葡萄球菌引起的感染，如肺炎、败血症等。尽管对严重感染疗效较差，但易引起细菌耐药性，因此宜与其他抗菌药物配伍使用。

新生霉素是从雪白链霉菌（Streptomyces niveus）的发酵中获得的一种抗生素，对抗青霉素耐药的葡萄球菌和某些变形杆菌有效。其抗菌作用在于抑制DNA复制，并通过干扰DNA解旋酶（拓扑异构酶）的作用来实现。

生物活性

Novobiocin钠盐（Albamycin、Cathomycin）是一种高效的细菌DNA旋转酶抑制剂，同时也是一种人体有机阴离子转运体，能够作用于hOAT1、hOAT3和hOAT4，其Ki值分别为14.87±0.40μM、4.77±1.12μM 和 90.50±7.50μM。

靶点

Target	Value
Topoisomerase II
Topoisomerase IV

体外研究

Novobiocin与Hsp90结合，改变了分子伴侣对geldanamycin和radicicol的亲和力，进而影响了依赖于Hsp90的关键调节激酶，包括V形Src、RAF-1和P185（ErbB2）在体内外水平上的表达。此外，Novobiocin还干扰共伴侣Hsc70和p23对Hsp90的结合，并以浓度依赖性方式特异性地抑制血红素调节eIF2α激酶（HRI）的成熟。

Novobiocin通过诱导Hsp90与CDC37从未成熟HRI解离，而Hsp90共分子伴侣P23、FKBP52和蛋白磷酸酶5仍然与未成熟HRI结合。这种作用导致了细胞形态和生化变化，进而引发细胞凋亡。

此外，Novobiocin作为HSP90抑制剂，能够降低SMYD3的表达，并剂量依赖性地抑制MDA-MB-231人乳腺癌细胞的增殖和迁移。它还能够通过下调SMYD3抑制乳腺癌细胞的迁移。

Novobiocin作为一种氨基酮类抗生素，干扰了热休克蛋白90（Hsp90）和缺氧诱导因子依赖基因表达的过程，从而损害了细胞的存活能力。在体外实验中，500 μM浓度的Novobiocin显著增加了胞内钙离子浓度、减少了前向散射、增强了膜联蛋白-V结合以及促进了ceramide的形成。

同时，它还能刺激红细胞死亡，这可能与细胞外Ca²⁺的进入和ceramide的产生有关。

反应信息

• 作为反应物：
  描述：

  sodium novobiocin 在 盐酸 作用下， 以 水 为溶剂， 以99.3%的产率得到新生霉素
  参考文献：
  名称：

  作为潜在的热休克蛋白90抑制剂的新霉素类似物的合成和生物学评估

  摘要：

  最近的研究表明，新霉素（NB）是具有证明的DNA回旋酶抑制作用的古默霉素（CA）家族的一种抗生素，通过与C-内的一个假定的ATP结合位点弱结合来抑制热休克蛋白90（HSP90）。总站。为了开发靶向该位点的更有效的HSP90抑制剂并定义此类化合物的结构-活性关系（SAR），我们合成了27种从NB和CA开始的3-amido-7-noviosylcoumarin类似物。使用几种生物学测定法评估了这些物质对HSP90抑制的证据，包括抑制细胞增殖和细胞周期阻滞，诱导热休克反应，抑制体外萤光素酶重新折叠以及消耗HSP90客户蛋白c-erbB-2 /。 HER-2 / neu（HER2）。这项SAR研究表明，通过除去NB / C-3上的吲哚-2-甲酰胺基团取代C-3上的4-羟基-异戊基苯甲酰胺基，可以显着提高生物活性。组从香豆素环。如化合物所示，香豆素部分中的4-羟基甲基化可适度提高生物活性11和13。

  DOI：

  10.1016/j.bmc.2013.06.042

文献信息

• Homodimeric Tobramycin Adjuvant Repurposes Novobiocin as an Effective Antibacterial Agent against Gram-Negative Bacteria
  作者：Temilolu Idowu、Derek Ammeter、Heather Rossong、George G. Zhanel、Frank Schweizer

  DOI：10.1021/acs.jmedchem.9b00876

  日期：2019.10.24

  is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that is nontoxic and more potent than the gold standard permeabilizing agent, polymyxin B nonapeptide. In pilot studies, the adjuvant

  跨膜的低渗透性是大多数抗生素对革兰氏阴性细菌无效的主要原因。渗透外膜的试剂通常在其有效浓度下是有毒的。在这里，我们报道了一种广谱同二聚妥布霉素佐剂的开发，该佐剂无毒且比金标准通透剂多粘菌素B九肽更有效。在先导研究中，佐剂可赋予新霉素抗革兰氏阴性细菌的有效杀菌活性，这些革兰氏阴性细菌包括带有质粒传播的mcr-的耐碳青霉烯和耐大肠菌素的菌株。1个基因。相对于单独的新霉素，对该组合的耐药性显着降低，并且没有诱导对其他抗生素（包括促旋酶作用的氟喹诺酮类药物）产生交叉耐药性。妥布霉素同型二聚体可允许使用较低剂量的新霉素，从而克服其双重功效和毒性问题。
• [EN] HOMODIMERIC TOBRAMYCIN ADJUVANT REPURPOSES NOVOBIOCIN AS AN EFFECTIVE ANTIBACTERIAL AGENT AGAINST GRAM-NEGATIVE BACTERIA<br/>[FR] NOVOBIOCINE ADAPTÉE D'ADJUVANT DE TOBRAMYCINE HOMODIMÈRE SERVANT D'AGENT ANTIBACTÉRIEN EFFICACE CONTRE DES BACTÉRIES À GRAM NÉGATIF
  申请人：UNIV MANITOBA

  公开号：WO2020232534A1

  公开（公告）日：2020-11-26

  Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that is non-toxic and more potent than the gold standard permeabilizing agent, polymyxin B nonapeptide. In pilot studies, the adjuvant confers potent bactericidal activity on novobiocin against Gram-negative bacteria, including carbapenem-resistant and colistin-resistant strains bearing plasmid-borne mcr-1 genes. Resistance development to the combination was significantly reduced, relative to novobiocin alone, and there was no induction of cross-resistance to other antibiotics, including the gyrase-acting fluoroquinolones. Tobramycin homodimer may allow the use of lower doses of novobiocin, overcoming its twin-problem of efficacy and toxicity.

  外膜的低渗透性是导致大多数抗生素对革兰氏阴性细菌无效的主要原因。渗透外膜的药物通常在有效浓度下具有毒性。在这里，我们报告了一种广谱同源二聚体托布拉霉素辅助剂的开发，该辅助剂无毒且比金标准的渗透剂多粘菌素B非肽更有效。在试点研究中，该辅助剂使新诺比信对革兰氏阴性细菌具有强效的杀菌活性，包括携带质粒编码mcr-1基因的碳青霉烯耐药和科利霉素耐药菌株。相对于单独使用新诺比信，对该组合的耐药发展显著减少，并且没有诱导对其他抗生素的交叉耐药，包括对DNA酶作用的氟喹诺酮类抗生素。托布拉霉素同源二聚体可能允许使用较低剂量的新诺比信，克服其疗效和毒性的双重问题。
• 60Co-Irradiation as an Alternate Method for Sterilization of Penicillin G, Neomycin, Novobiocin, and Dihydrostreptomycin
  作者：Kiyoshi Tsuji、Paul D. Rahn、Kathy A. Steindler

  DOI：10.1002/jps.2600720106

  日期：1983.1

  To determine the radiolytic degradation scheme and the stability of the antibiotics following irradiation, high-performance liquid chromatographic (HPLC) methods were developed. The resulting rates of degradation for the antibiotics were 0.6, 1.2, 2.3, and 0.95%/Mrad for penicillin G, neomycin, novobiocin, and dihydrostreptomycin, respectively. Furthermore, radiolytic degradation pathways for the antibiotics

  评估了使用60Co辐照对抗生素进行灭菌的效果。抗生素粉末仅偶尔被微生物污染。对于曲霉菌属（UC 7297、7298），烟曲霉（UC 7299），杜鹃花属（UC 7300），产品和环境分离物的D值分别为0.028、0.027、0.015、0.046、0.15、0.018和0.19 Mrads。 ，草酸青霉（UC 7269），麦芽假单胞菌（UC 6855）和生物学指示微生物，短小芽孢杆菌孢子（ATCC 27142）。因此，1.14 Mrads的辐照剂量足以实现对短双歧杆菌芽孢的六对数循环破坏。根据生物负荷数据，计算得出最小辐照剂量为1.05 Mrads，足以获得对最耐辐射的分离物Pen进行灭菌的10（-6）概率。草酸 为了确定辐射降解方案和辐射后抗生素的稳定性，开发了高效液相色谱（HPLC）方法。青霉素G，新霉素，新霉素和二氢链霉素的抗生素降解率分别为0.6、1.2、2.3和0.95％/ Mr
• New Novobiocin Analogues as Antiproliferative Agents in Breast Cancer Cells and Potential Inhibitors of Heat Shock Protein 90
  作者：Gaëlle Le Bras、Christine Radanyi、Jean-François Peyrat、Jean-Daniel Brion、Mouâd Alami、Véronique Marsaud、Barbara Stella、Jack-Michel Renoir

  DOI：10.1021/jm0707774

  日期：2007.11.1

  positions of coumarin which appeared to be essential for degradation of hsp90 client proteins. Removal of the noviose moiety in novobiocin together with introduction of a tosyl substituent at C-4 or C-7 coumarins provides 6e and 6f as lead structures which compared favorably with novobiocin as demonstrated by enhanced rates of cell death. The processing and activation of caspases 7 and 8 and the subsequent

  选择性hsp90抑制剂可同时破坏和消耗参与细胞增殖和存活，血管生成和转移的关键信号蛋白。作为hsp90的新型抑制剂，缺少诺维糖部分的新霉素类似物已进行了研究。已经产生了一系列新的3-氨基香豆素类似物，并在细胞增殖中进行了筛选，并且通过在人乳腺癌细胞中消耗雌激素受体，HER2，Raf-1和cdk4来评估hsp90抑制的分子标记。这项结构-活性关系研究强调了香豆素的C-4和/或C-7位置的关键作用，这对hsp90客户蛋白的降解至关重要。除去新霉素中的新葡糖部分，并在C-4或C-7香豆素上引入甲苯磺酰基取代基，可提供6e和6f作为前导结构，与新霉素相比，有利于细胞死亡率的提高。半胱氨酸蛋白酶7和8的加工和激活以及随后的6e对PARP的切割表明刺激了外在凋亡途径。
• Novobiocin Enhances Polymyxin Activity by Stimulating Lipopolysaccharide Transport
  作者：Michael D. Mandler、Vadim Baidin、James Lee、Karanbir S. Pahil、Tristan W. Owens、Daniel Kahne

  DOI：10.1021/jacs.8b02283

  日期：2018.6.6

  Gram-negative bacteria are challenging to kill with antibiotics due to their impenetrable outer membrane containing lipopolysaccharide (LPS). The polymyxins, including colistin, are the drugs of last resort for treating Gram-negative infections. These drugs bind LPS and disrupt the outer membrane; however, their toxicity limits their usefulness. Polymyxin has been shown to synergize with many antibiotics

  革兰氏阴性细菌很难用抗生素杀死，因为它们的外膜含有脂多糖 (LPS)，难以穿透。多粘菌素，包括粘菌素，是治疗革兰氏阴性菌感染的最后手段。这些药物结合 LPS 并破坏外膜；然而，它们的毒性限制了它们的用途。多粘菌素已被证明可以与许多抗生素产生协同作用，包括新生霉素，它可以抑制 DNA 旋转酶，促进这些抗生素穿过外膜的转运。最近，我们发现新生霉素不仅能抑制 DNA 旋转酶，还能结合并刺激 LptB（一种为 LPS 运输提供动力的 ATP 酶）。在这里，我们报道了分离这两种活性的新生霉素衍生物的合成。一种类似物保留了 LptB 刺激活性，但无法抑制 DNA 旋转酶。这种类似物本身无毒，但通过结合 LptB 并刺激 LPS 转运来增强多粘菌素的杀伤力。因此，LPS 转运激动作用对新生霉素-多粘菌素协同作用有很大贡献。我们还报道了其他新生霉素类似物，它们对 DNA 旋转酶的抑制效果优于或等于新生霉素，但与