Verteporfin
(Synonyms: 维替泊芬; CL 318952) 目录号 : GC14482
维替泊芬是一种有效的 PD-L1 表达抑制剂，用于治疗年龄相关性黄斑变性、鲜红斑痣和癌症。
Cas No.:129497-78-5
Sample solution is provided at 25 µL, 10mM.
Verteporfin is a potent inhibitor of PD-L1 expression used for treatment in the age-related macular degeneration , port-wine stain birthmarks and cancer.[1]
In vitro experiment it shown that at 1μM versus 0.5 μM concentrations of verteporfin, it was sufficient to decrease PD-L1 expression in ATG5 depleted cells.[1] In vitro, at very low concentrations of verteporfin (0.1–0.2 μm) , verteporfin induced significant cell death in GSCs. However, 0.5 μm verteporfin had no effect on the cell death in differentiated GSCs, IMR90, rat NSCs or mouse astrocytes.[2] In vitro efficacy test it indicated treatment with 4, 8 and 12?μM verteporfin decreased significantly the expression levels of YAP, AXL and CYR61 mRNA in MCF-7, BT-474 and BT-549 cells. And verteporfin also downregulated the mRNA expression of CTGF in BT-474 and BT-549 cells.[3] Treatment with 0.5, 1, 2, and 5 μM verteporfin inhibited the viability of HeLa cells and had no obvious effect on H8 cells.[4]
In vivo study it demonstrated that treatment with 2 mg.kg-1 free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. However, mice were treated 8 mg.kg-1 nanostructured lipid carriers-verteporfin intravenously laser light exposure of tumors significantly inhibited tumor growth without visible toxicity.[5] In vivo, 2 mg/kg verteporfin infusion alone resulted in nitric oxide and malonyldialdehyde level increments in the retina.[6]
References:
[1].Liang J, et al. Verteporfin Inhibits PD-L1 through Autophagy and the STAT1-IRF1-TRIM28 Signaling Axis, Exerting Antitumor Efficacy. Cancer Immunol Res. 2020 Jul;8(7):952-965. Kuramoto K, Yamamoto M, Suzuki S, Sanomachi T, Togashi K, Seino S, Kitanaka C, Okada M.
[2].Kuramoto K, et al. Verteporfin inhibits oxidative phosphorylation and induces cell death specifically in glioma stem cells. FEBS J. 2020 May;287(10):2023-2036.
[3].Wei C, Li X. Verteporfin inhibits cell proliferation and induces apoptosis in different subtypes of breast cancer cell lines without light activation. BMC Cancer. 2020 Oct 29;20(1):1042.
[4].Yin L, Chen G. Verteporfin Promotes the Apoptosis and Inhibits the Proliferation, Migration, and Invasion of Cervical Cancer Cells by Downregulating SULT2B1 Expression. Med Sci Monit. 2020 Oct 20;26:e926780.
[5].Michy T, et al. Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo. Cancers (Basel). 2019 Nov 8;11(11):1760.
[6].Turkuoglu P, et al. Retinal nitric oxide and malonyldialdehyde levels following photodynamic therapy. Indian J Ophthalmol. 2011 Jan-Feb;59(1):5-8.
维替泊芬是一种有效的 PD-L1 表达抑制剂,用于治疗年龄相关性黄斑变性、鲜红斑痣和癌症。[1]
体外实验表明,在 1μM 和 0.5μM 浓度的维替泊芬中,足以降低 ATG5 耗尽细胞中的 PD-L1 表达。[1] 在体外,在非常低的浓度下维替泊芬 (0.1-0.2 μm),维替泊芬在 GSC 中诱导显着的细胞死亡。然而,0.5 μm维替泊芬对分化的GSCs、IMR90、大鼠NSCs或小鼠星形胶质细胞的细胞死亡没有影响。[2] 体外药效试验表明,4、8和12μM维替泊芬处理降低YAP、AXL和CYR61 mRNA在MCF-7、BT-474和BT-549细胞中的表达水平显着升高。维替泊芬也下调BT-474和BT-549细胞中CTGF mRNA的表达。[3]0.5、1、2和5 μM维替泊芬抑制HeLa细胞的活力并且没有对H8细胞有明显作用。[4]
体内研究表明,用 2 mg.kg-1 的游离维替泊芬治疗会引起严重的光毒性副作用,导致 8 只小鼠中有 5 只死亡。然而,小鼠接受 8 mg.kg-1 纳米结构脂质载体-维替泊芬静脉注射,激光照射肿瘤显着抑制肿瘤生长,且无可见毒性。[5] 在体内,单独输注 2 mg/kg 维替泊芬导致视网膜中的一氧化氮和丙二醛水平增加。[6]
| Cell experiment [1]: | |
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Cell lines |
RAW 264.7 cells |
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Preparation Method |
RAW 264.7 cells were pretreated with 2 μM verteporfin for 2 h, then stimulated with LPS (1 μg/ml) for 22 h. |
|
Reaction Conditions |
2 μM; 2 h |
|
Applications |
When RAW 264.7 cells were treated with 2 μM verteporfin, GCSF, IL-6, CCL2, MCP-5, CCL5, and TNF-α were significantly inhibited compared with cells treated with LPS alone. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice |
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Preparation Method |
Lewis lung carcinoma cells (LLCs, 5 x 105 in 100 μl phosphate-buffered saline) were inoculated subcutaneously into C57BL/6 mice (male, 8–12 weeks) in both flanks. Five days after inoculation, mice were randomly divided into 4 groups and treated with vehicle, BMN 673 0.33 mg/Kg daily (oral gavage), verteporfin 30 mg/kg daily (intraperitoneal injection) and the combination of BMN 673 with verteporfin for 16 days. Tumors size were measured every 2 days by digital calipers to determine tumor volume using the formula [length/2] × [width2]. |
|
Dosage form |
30 mg/kg; i.p. |
|
Applications |
Verteporfin treatment led to marked decreases in PD-L1 expression and increases in CD8 T cells especially in the combinatorial group of vereporfin and BMN 673. |
|
References: [1]. Wang Y, Wang L, Wise JTF, Shi X, Chen Z. Verteporfin inhibits lipopolysaccharide-induced inflammation by multiple functions in RAW 264.7 cells. Toxicol Appl Pharmacol. 2020 Jan 15;387:114852. [2]. Liang J, et al. Verteporfin Inhibits PD-L1 through Autophagy and the STAT1-IRF1-TRIM28 Signaling Axis, Exerting Antitumor Efficacy. Cancer Immunol Res. 2020 Jul;8(7):952-965. |
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| Cas No. | 129497-78-5 | SDF | |
| 别名 | 维替泊芬; CL 318952 | ||
| Canonical SMILES | O=C([C@H]1[C@](/C(N=C2/C=C(C(C)=C/3C=C)\NC3=C/C4=N/C(C(CCC(O)=O)=C4C)=C\5)=C/C6=C(C)C(CCC(OC)=O)=C5N6)(C)C2=CC=C1C(OC)=O)OC | ||
| 分子式 | C41H42N4O8 | 分子量 | 718.79 |
| 溶解度 | ≥ 18.3mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品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产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3912 mL | 6.9561 mL | 13.9123 mL |
| 5 mM | 0.2782 mL | 1.3912 mL | 2.7825 mL |
| 10 mM | 0.1391 mL | 0.6956 mL | 1.3912 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
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