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]. |
| 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) |
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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%. |
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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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| 结构分类 | - Antibiotics
- Other Antibiotics
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| 来源 | Streptomyces diastatochromogenes |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 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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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% DMSO 90% (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% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (8.58 mM); Clear solution
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