Verteporfin
(Synonyms: 维替泊芬; CL 318952) 目录号 : GC14482
A photosensitizer
Cas No.:129497-78-5
Sample solution is provided at 25 µL, 10mM.
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| 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. |
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Reaction Conditions |
2 μM; 2 h |
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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]. |
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Dosage form |
30 mg/kg; i.p. |
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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. |
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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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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]
| 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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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 |
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动物平均体重 | g | |
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动物数量 | 只 |
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2.
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Verteporfin Inhibits PD-L1 through Autophagy and the STAT1-IRF1-TRIM28 Signaling Axis, Exerting Antitumor Efficacy
Programmed cell death 1 ligand 1 (PD-L1) is a key driver of tumor-mediated immune suppression, and targeting it with antibodies can induce therapeutic responses. Given the costs and associated toxicity of PD-L1 blockade, alternative therapeutic strategies are needed. Using reverse-phase protein arrays to assess drugs in use or likely to enter trials, we performed a candidate drug screen for inhibitors of PD-L1 expression and identified verteporfin as a possible small-molecule inhibitor. Verteporfin suppressed basal and IFN-induced PD-L1 expression in vitro and in vivo through Golgi-related autophagy and disruption of the STAT1-IRF1-TRIM28 signaling cascade, but did not affect the proinflammatory CIITA-MHC II cascade. Within the tumor microenvironment, verteporfin inhibited PD-L1 expression, which associated with enhanced T-lymphocyte infiltration. Inhibition of chromatin-associated enzyme PARP1 induced PD-L1 expression in high endothelial venules (HEV) in tumors and, when combined with verteporfin, enhanced therapeutic efficacy. Thus, verteporfin effectively targets PD-L1 through transcriptional and posttranslational mechanisms, representing an alternative therapeutic strategy for targeting PD-L1.
Melatonin and verteporfin synergistically suppress the growth and stemness of head and neck squamous cell carcinoma through the regulation of mitochondrial dynamics
The prevalence of head and neck squamous cell carcinoma (HNSCC) has continued to rise for decades. However, drug resistance to chemotherapeutics and relapse, mediated by cancer stem cells (CSCs), remains a significant impediment in clinical oncology to achieve successful treatment. Therefore, we focused on analyzing CSCs in HNSCC and demonstrated the effect of melatonin (Mel) and verteporfin (VP) on SCC-25 cells. HNSCC CSCs were enriched in the reactive oxygen species-low state and in sphere-forming cultures. Combination treatment with Mel and VP decreased HNSCC viability and increased apoptosis without causing significant damage to normal cells. Sphere-forming ability and stem cell population were reduced by co-treatment with Mel and VP, while mitochondrial ROS level was increased by the treatment. Furthermore, the expression of mitophagy markers, parkin and PINK1, was significantly decreased in the co-treated cells. Mel and VP induced mitochondrial depolarization and inhibited mitochondrial function. Parkin/TOM20 was localized near the nucleus and formed clusters of mitochondria in the cells after treatment. Moreover, Mel and VP downregulated the expression of markers involved in epithelial-mesenchymal transition and metastasis. The migration capacity of cells was significantly decreased by co-treatment with Mel and VP, accompanied by the down-regulation of MMP-2 and MMP-9 expression. Taken together, these results indicate that co-treatment with Mel and VP induces mitochondrial dysfunction, resulting in the apoptosis of CSCs. Mel and VP could thus be further investigated as potential therapies for HNSCC through their action on CSCs.
Verteporfin synergizes the efficacy of anti-PD-1 in cholangiocarcinoma
Background: Cholangiocarcinoma (CCA) is one of the primary hepatobiliary malignant neoplasms with only 10% of 5-year survival rate. Promising immunotherapy with the blockade of immune checkpoints has no clear benefit in CCA. The inhibition of YAP1 signaling by verteporfin has shown encouraging results by inhibiting cell proliferation and inducing apoptosis. This study aimed to evaluate the potential benefit of the combination of verteporfin and anti-programmed cell death 1 (PD-1) in CCA mouse model.
Methods: We assessed the cytotoxicity of verteporfin in human CCA cell lines in vitro, including both intrahepatic CCA and extrahepatic CCA cells. We examined the in vitro effect of verteporfin on cell proliferation, apoptosis, and stemness. We evaluated the in vivo efficacy of verteporfin, anti-PD-1, and a combination of both in subcutaneous CCA mouse model.
Results: Our study showed that verteporfin reduced tumor cell growth and enhanced apoptosis of human CCA tumor cells in vitro in a dose-dependent fashion. Nevertheless, verteporfin impaired stemness evidenced by reduced spheroid formation and colony formation, decreased numbers of cells with aldehyde dehydrogenase activity and positive cancer stem cell markers (all P < 0.05). The combination of verteporfin and anti-PD-1 reduced tumor burden in CCA subcutaneous SB1 tumor model compared to either agent alone.
Conclusions: Verteporfin exhibits antitumor effects in both intrahepatic and extrahepatic CCA cell lines and the combination with anti-PD-1 inhibited tumor growth.
Verteporfin PDT for non-standard indications--a review of current literature
Background: Verteporfin photodynamic therapy (PDT) is approved for the treatment of predominantly classic subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), as well as for subfoveal CNV due to pathologic myopia and ocular histoplasmosis syndrome. Verteporfin PDT addresses the underlying pathology of ocular vascular disorders through its angio-occlusive mechanism of action, which reduces both visual acuity loss and the underlying leakage associated with lesions. Verteporfin PDT has also been associated with encouraging treatment outcomes in case studies involving patients with choroidal vascular disorders such as polypoidal choroidal vasculopathy, central serous chorioretinopathy, choroidal haemangioma, angioid streaks, and inflammatory CNV, i.e. conditions currently considered as non-standard indications of verteporfin PDT. In many studies, outcomes were better than expected based on the natural courses of each of these conditions. Although the anti-vascular endothelial growth factor (VEGF) therapies, ranibizumab and pegaptanib, have been approved for CNV due to AMD, their role in these other choroidal vascular disorders remains to be established. We summarize current literature that has documented the use of verteporfin PDT in these conditions.
Conclusions: The complex pathogenesis of CNV provides a rationale for investigating combination approaches comprising verteporfin PDT and anti-VEGF therapies. Randomized controlled studies are warranted to confirm the preliminary results of verteporfin PDT as a monotherapy or in combination with anti-VEGF therapies in the treatment of a variety of choroidal vascular conditions.