Toyocamycin (Vengicide) 是链霉菌类产生的腺苷类似物，是 X 盒结合蛋白 1 (
XBP1) 抑制剂。Toyocamycin 可阻断 RNA 合成和核糖体功能，并诱导凋亡 (
apoptosis)。Toyocamycin 影响 IRE1α-XBP1 通路，抑制 XBP1 mRNA 断裂 (
IC50=80 nM)，不影响 IRE1α 自身磷酸化。Toyocamycin 特异性抑制
CDK9，
IC50为 79 nM。
| 生物活性 |
Toyocamycin (Vengicide) is an adenosine analog produced byStreptomyces diastatochromogenes, acts as anXBP1inhibitor. Toyocamycin blocks RNA synthesis and ribosome function, and inducesapoptosis. Toyocamycin affects IRE1α-XBP1 pathway, and inhibits XBP1 mRNA cleavage with anIC50value of 80 nM with affecting IRE1α auto-phosphorylation. Toyocamycin specifically inhibitsCDK9with anIC50value of 79 nM[1][2][3].
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| IC50& Target |
CDK9/cyclinT1 79 nM (IC50) |
CDK7/Mat1/cyclinH1 2.8 μM (IC50) |
CDK2/cyclinA 0.67 μM (IC50) |
Cdk4/cyclin D3 15 μM (IC50) |
cdk6/cyclin D3 >10 μM (IC50) |
|
体外研究
(In Vitro) |
Toyocamycin (0-0.3 μM; 4 h) inhibits ER stress-induced XBP1 mRNA splicing, and selectively inhibits the ER stress-induced activation of the IRE1α-XBP1 pathway[1].
Toyocamycin (0-0.3 μM; 24 h) inhibits constitutive activation of XBP1 in MM cell lines[1].
Toyocamycin (250 nM; 48 h) inhibits CDK9 enzymatic activity in colon cancer cell lines[2].
Toyocamycin (0.05 nM-50 μM; 48 h and 72 h) doesn’t trigger immediate cytotoxicity against YB5 and HCT116 cells with cell viability above 50%, but results eradication of cancer cells 2 weeks later at 10 nM for 24 h treatment[2].
Toyocamycin (0-100 nM; 24 or 48 h) induces apoptosis via mitochondrial pathway in PC-3 cells[3].
Toyocamycin (60 nM; 0-48 h) promotes p38/ERK MAPK activation and regulates ROS-mediated apoptosis by inhibition of p38 on ERK MAPK[3].
Western Blot Analysis[1]
| Cell Line: |
HeLa, HEK293 |
| Concentration: |
0, 0.03, 0.1, 0.3 μM |
| Incubation Time: |
4 hours |
| Result: |
Suppressed neither tunicamycin-induced ATF6 nor PERK activation.
Inhibited IRE1α-induced XBP1 mRNA cleavage without affecting IRE1α phosphorylation on Ser724. |
Western Blot Analysis[3]
| Cell Line: |
Human prostate cancer PC-3 cells |
| Concentration: |
60 nM |
| Incubation Time: |
12, 24, 36, 48 hours |
| Result: |
Suppressed the phosphorylation level of AKA, while decreasing the phosphorylation level of ERK and p38. |
Cell Viability Assay[3]
| Cell Line: |
PC-3 and RWPE-1 cells |
| Concentration: |
0, 20, 40, 60, 80, 100 nM |
| Incubation Time: |
24 or 48 hours |
| Result: |
Inhibted cell viability and induced cell apoptosis by 62%. |
|
体内研究
(In Vivo) |
Toyocamycin (0.5 mg/kg, 1.0 mg/kg; i.p.; twice a week; 2 weeks) shows anti-tumor activity in a xenograft model with human multiple myeloma (MM) cells, while the anti-tumor effect enhanced byBortezomib(HY-10227)[1].
| Animal Model: |
SCID mice injected with human multiple myeloma (MM) cells[1] |
| Dosage: |
0.5 mg/kg, 1.0 mg/kg |
| Administration: |
Intraperitoneal injection; twice a week; 2 weeks |
| Result: |
Reduced the tumor volume significantly. Showed enhancing anti-tumor activity represented as smaller tumor volumes when compared withBortezomib(HY-10227). |
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| 分子量 |
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| 性状 |
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| Formula |
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| CAS 号 |
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| 中文名称 |
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| 结构分类 |
- Antibiotics
- Other Antibiotics
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| 来源 |
Streptomyces diastatochromogenes
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
| Powder |
-20°C |
3 years |
| In solvent |
-80°C |
6 months |
|
-20°C |
1 month |
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| 溶解性数据 |
In Vitro:
DMSO : 100 mg/mL(343.34 mM;Need ultrasonic)
配制储备液
| 1 mM |
3.4334 mL |
17.1668 mL |
34.3336 mL |
| 5 mM |
0.6867 mL |
3.4334 mL |
6.8667 mL |
| 10 mM |
0.3433 mL |
1.7167 mL |
3.4334 mL |
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请根据半岛bd体育手机客户端 在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的半岛bd体育手机客户端 失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶
-
1.
请依序添加每种溶剂： 10% DMSO40%PEG3005%Tween-8045% saline
Solubility: ≥ 2.5 mg/mL (8.58 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.58 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
-
2.
请依序添加每种溶剂： 10% DMSO90% (20%SBE-β-CDin saline)
Solubility: ≥ 2.5 mg/mL (8.58 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.58 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
-
3.
请依序添加每种溶剂： 10% DMSO90%corn oil
Solubility: ≥ 2.5 mg/mL (8.58 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.58 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
*
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