12,15-Dihydroxy-7-methyl-8-oxabicyclo[11.3.0]hexadeca-2,10-dien-9-one | 20350-15-6

• 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 - 大环内酯类和类似物
• 英文名称: 12,15-Dihydroxy-7-methyl-8-oxabicyclo[11.3.0]hexadeca-2,10-dien-9-one
• 英文别名: 2,15-dihydroxy-7-methyl-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-5-one
• CAS: 20350-15-6
• 化学式: C₁₆H₂₄O₄
• 分子量: 280.36
• InChiKey: KQNZDYYTLMIZCT-UHFFFAOYSA-N

物化性质

• 熔点：
  200-205 °C
• 比旋光度：
  93 º (C=2 IN MEOH)
• 沸点：
  492.7±45.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)
• 闪点：
  87 °C
• 溶解度：
  甲醇：10 mg/mL，澄清，无色至淡黄色
• 稳定性/保质期：

  常温常压下稳定，避免接触强氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn,T
• 安全说明：
  S24/25,S26,S36,S45
• 危险类别码：
  R25
• WGK Germany：
  3
• 海关编码：
  29411090
• 危险品运输编号：
  UN 2811 6
• RTECS号：
  GY8410000
• 储存条件：
  | 2-8℃ |

SDS

Name:	Brefeldin A Natural Material Safety Data Sheet
Synonym:
CAS:	20350-15-6

Section 1 - Chemical Product MSDS Name:Brefeldin A Natural Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
20350-15-6	Brefeldin A, Natural	100%	unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or 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:

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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. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Vapors may be heavier than air. They can spread along the ground and collect in low or confined areas.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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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. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Keep refrigerated. (Store below 4C/39F.)

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 20350-15-6: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
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.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 203.00 - 204.00 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C16H24O4
Molecular Weight: 280.35

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 20350-15-6: GY8410000 LD50/LC50:
Not available.
Carcinogenicity:
Brefeldin A, Natural - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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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.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
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# 20350-15-6: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 20350-15-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 20350-15-6 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Brefeldin A 作用于 HCT 116 细胞，抑制 ATPase 和蛋白运输（protein tRAnSPort），IC50 值为 0.2 μM。它能诱导癌细胞分化和凋亡，并提高同源重组修复效率，作为 CRISPR-mediated HDR 的增强剂。Brefeldin A 同时也是自噬和线粒体自噬的抑制剂。

靶点

Target	Value
ATPase (HCT 116)	0.2 μM

体外研究

Brefeldin A 是一种真菌代谢产物，能抑制内质网和高尔基体之间的传输。处理 HCT 116 人结肠癌细胞后，观察到形态学变化，表明细胞分化。主要通过诱导分化和凋亡发挥其细胞毒性作用。20 μg/mL Brefeldin A 处理检测条 6 小时，在 10 mM Indomethacin 和 30 μM L-NOARG 存在时，完全废除 BRAdykinin 引起的松弛现象。

浓度为 1 nM 到 1 mM 的 20 μg/mL Brefeldin A 处理可以废除 BRAdykinin 引起的 [Ca^2+ ]i 升高。Brefeldin A 不影响 GTPS 与 myr-RARF1 自发磷脂依赖性的结合，但完全废除了视网膜等渗提取物（RIE）的催化交换功能，其半抑制浓度为 2 μM。Brefeldin A 抑制多种膜转运途径，并作用于高尔基体膜或脑细胞质，抑制 ADP-核糖基化因子特定的鸟嘌呤核苷酸交换活性。

Brefeldin A 完全抑制了视网膜提取物中的 ARF 特定的鸟嘌呤核苷酸交换因子。即使浓度高达 300 μM，Brefeldin A 只部分抑制 ADP-核糖基化因子（ARFs）释放的视网膜等渗提取物催化的 GTPS 活性。

Brefeldin A 诱导高尔基体与 ER 融合，并废除了 CERT 抑制剂 HPA-12 的抑制效果。处理 CHO 细胞后，鞘磷脂合成增加 2 到 3 倍。Brefeldin A 还能引起 B-CLL、多发性骨髓瘤（U266、NCI-H929）、JURKAT、HeLa 细胞，白血病（HL60、K562、BJAB）、结肠（HT-29）及前列腺和腺样囊性瘤细胞的凋亡。25 ng/mL Brefeldin A 处理 HF4.9 和 HF28RA 细胞可完全抑制其生长，而 HF1A3 需要更高剂量 (75 ng/mL) 才能完全抑制生长。在 50-75 ng/mL 浓度下处理 HF1A3、HF4.9 和 HF28RA 细胞 24 小时后，其细胞增殖受到抑制，并表现出剂量依赖性。

用途

Brefeldin A 是一种常用的蛋白转运抑制剂，特异性地可逆地阻断蛋白质从内质网(ER)向高尔基体 (Golgi) 的转运。处理后，高尔基体会快速被破坏并融合到内质网上，该过程呈能量、温度和微管依赖性。在哺乳动物和酵母中，Brefeldin A 对蛋白从内质网向高尔基体转运的抑制可能是通过一类可以激活 Arf1p GTPase 的 GTP-exchange factors 实现的。Arf1p 通过招募 cOAt proteins 到细胞内膜形成转运小泡。

文献信息

• Inhibition of intimal hyperplasia using antibodies to PDGF receptors
  申请人：——

  公开号：US20020044933A1

  公开（公告）日：2002-04-18

  Methods for inhibiting intimal hyperplasia in the vasculature of mammals, including primates, are disclosed. The methods comprise administering to the mammal an anti-PDGF receptor antibody, such as an anti-PDGF-alpha receptor antibody or an anti-PDGF-beta receptor antibody. The methods are useful in reducing intimal hyperplasia due to, for example, vascular injuries resulting from angioplasty, endarterectomy, reduction atherectomy or anastomosis of a vascular graft. The anti-PDGF receptor antibodies may optionally be administered coordinately with heparin, whereby the coordinately administered antibody and heparin are combinatorially effective in inhibiting intimal hyperplasia.

  本发明公开了抑制哺乳动物（包括灵长类动物）血管内膜增生的方法。这些方法包括向哺乳动物施用抗 PDGF 受体抗体，如抗 PDGF-α 受体抗体或抗 PDGF-beta 受体抗体。这些方法可用于减少血管内膜增生，例如血管成形术、动脉内膜切除术、还原性动脉粥样硬化切除术或血管移植吻合术造成的血管损伤。抗 PDGF 受体抗体可选择性地与肝素协同给药，这样协同给药的抗体和肝素在抑制血管内膜增生方面具有组合效果。
• Ein Verfahren zur Herstellung von halogenierten Ethern
  申请人：Säurefabrik Schweizerhall

  公开号：EP0679627B1

  公开（公告）日：1998-09-09
• COMPOSITION FOR INHIBITING INTIMAL HYPERPLASIA USING PDGF ANTAGONISTS AND HEPARIN
  申请人：ZymoGenetics, Inc.

  公开号：EP0801572A2

  公开（公告）日：1997-10-22
• USE OF BREFELDIN A AND DERIVATIVES THEREOF IN THE PREPARATION OF MEDICAMENTS FOR THE TREATMENT OF HYPERPLASIA AND RELATED DISORDERS
  申请人：ZymoGenetics, Inc.

  公开号：EP0831807B1

  公开（公告）日：2005-12-21
• COMPOSITIONS AND METHODS FOR PROTECTING ORGANS, TISSUE AND CELLS FROM IMMUNE SYSTEM-MEDIATED DAMAGE
  申请人：THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

  公开号：EP1107789B1

  公开（公告）日：2008-06-25