Verteporfin, a benzoporphyrin derivative monoacid ring A, can inhibit the activity of YAP.

Verteporfin在体内代谢为活性较低的形式,并且迅速清除,主要通过粪便排出,一小部分通过尿液排泄.Verteporfin疗法有效和有选择地防止荧光素染料从实验诱导的猴子中的CNV泄漏.Verteporfin在建立的兔子眼睛的脉络膜脉管系统,RPE以及光感受器中迅速积累.给小鼠静脉注射3小时后,Verteporfin达到最大组织水平,随后在24小时内迅速下降.

Verteporfin与LDL结合形成一个复合物,随后可能通过LDL受体或者內吞作用被增殖细胞 (例如,新生血管内皮细胞) 摄取。Verteporfin疗法在选择性内皮损伤后通过血管通道的血栓形成实现血管腔室的完全血管造影闭塞。如光学和电子显微镜所示,Verteporfin疗法选择性诱导可再生的和离体的脉络膜毛细血管闭塞,而不改变覆盖的光感受器或神经节细胞。Verteporfin与光共同快速表现凋亡变化,通过caspase-3和caspase-9激活以及HL-60细胞中PARP的裂解表现,这些变化被普通半胱天冬酶抑制剂ZVAD.fmk所阻断。

Cells (5 × 103) are plated in 96 well plates. Cells are treated the next day for 24 to 48 hours and then assessed for caspase-3 activity by Caspase-Glo-3/7 Assay, as per manufacturer's instructions and a luminescence plate reader.

Verteporfin is dissolved in DMSO. PDX cells co-cultured with S17 cells are treated with 16 combinations of verteporfin (60 nM, 120 nM, 180 nM, and 240 nM) and dasatinib (12 nM, 24 nM, 36 nM, and 48 nM). The viabilities of cells treated with each combination are measured after 48 h using FACS Aria flow cytometer. In order to estimate drug interaction between verteporfin and dasatinib, a normalized isobologram and fraction affectedcombination index (CI) plot are made using CompuSyn software. CI values greater than 1.0 indicated antagonistic effects, equal to 1.0 additive effects, and below 1.0 synergistic effects.

129497-78-5

C82H84N8O16

1437.614

CL 318952;BPD-MA;维替泊芬;Verteporfin

[1]Schmidt-Erfurth U, et al. Surv Ophthalmol, 2000, 45(3), 195-214. [2]Isfort I, Elges S, Cyra M, et al. Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone[J]. Scientific Reports. 2019, 9(1): 1-9. [3]Peng G, Suo S, Cui G, et al. Molecular architecture of lineage allocation and tissue organization in early mouse embryo[J]. Nature. 2019, 572(7770): 528-532. [4]Zhuang Q, Li F, Liu J, et al. Nuclear exclusion of YAP exacerbates podocyte apoptosis and disease progression in Adriamycin-induced focal segmental glomerulosclerosis[J]. Laboratory Investigation. 2021, 101(2): 258-270. [5]Ilka Isfort, Magdalene Cyra, Sandra Elges, Sareetha Kailayangiri, Bianca Altvater, Claudia Rossig, Konrad Steinestel et al. SS18-SSX-dependent YAP/TAZ Signaling in Synovial Sarcoma [J]. Clinical Cancer Research. 2019 Feb 27: clincanres-3553. [6]Liu-Chittenden Y, et al. Genes Dev. 2012, 26(12):1300-5. [7]Marcel Trautmann, Ya-Yun Cheng, Patrizia Jensen, Ninel Azoitei, Ines Brunner, Jennifer Hüllein, Mikolaj Slabicki et al. Requirement for YAP1 signaling in myxoid liposarcoma [J]. EMBO molecular medicine. 2019 May;11(5): e9889. [8]Granville DJ, et al. Blood, 2000, 95(1), 256-262. [9]Tang Y, Fang G, Guo F, et al. Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer[J]. Cancer Cell. 2020, 38(1): 115-128. e9.

[1]Peng G, Suo S, Cui G, et al. Molecular architecture of lineage allocation and tissue organization in early mouse embryo. Nature. 2019, 572(7770): 528-532. [2]Tang Y, Fang G, Guo F, et al. Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer. Cancer Cell. 2020, 38(1): 115-128. e9. [3]Isfort I, Cyra M, Elges S, et al. SS18-SSX-dependent YAP/TAZ Signaling in Synovial Sarcoma. Clinical Cancer Research. 2019, 25(12): 3718-3731 [4]Trautmann M, Cheng Y Y, Jensen P, et al. Requirement for YAP1 signaling in myxoid liposarcoma. EMBO Molecular Medicine. 2019, 11(5): e9889 [5]Zhuang Q, Li F, Liu J, et al. Nuclear exclusion of YAP exacerbates podocyte apoptosis and disease progression in Adriamycin-induced focal segmental glomerulosclerosis. Laboratory Investigation. 2021, 101(2): 258-270. [6]Isfort I, Elges S, Cyra M, et al. Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone. Scientific Reports. 2019, 9(1): 1-9

H2O:<1 mg/mL
Ethanol:<1 mg/mL
DMSO:93 mg/mL (129.4 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years