Verteporfin (CL 318952) [129497-78-5]

Biological Activity

Verteporfin (CL 318952) is a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as age-related macular degeneration. Verteporfin (CL 318952) is a YAP inhibitor that disrupts YAP-TEAD interactions, and it is also an inhibitor of autophagy that blocks autophagy at an early stage by inhibiting autophagosome formation.

Verteporfin is specifically selected by PDX-cell screening. The concentrations to cause 50% growth inhibition (GI50) for PhLO, PhLH, and PhLK are 228 nM, 395 nM, and 538 nM, respectively, whereas GI50 for ALL-1, TCC-Y/sr, and NPhA1 are 3.93 µM, 2.11 µM, and 5.61 µM, respectively. GSH significantly reduces the sensitivity of 2 out of 3 PDX cells to verteporfin. Verteporfin reduces the mitochondrial membrane potential in PDX cells.

Verteporfin reduces the PTX-resistance on HCT-8/T cells by inhibiting YAP expression and combination therapy with verteporfin and NSC 125973 shows synergism on inhibition of YAP and cytotoxicity to HCT-8/T.

Protocol (for reference only)

Cell Experiment
Cell lines	GBM cells
Preparation method	To investigate VP activation a Lumenis Opal PDT Laser with Haag slit lamp adapter containing a laser system diode with continuous-wave solid-state laser, the wavelength of 689 ± 3 nm, was used, which is usually applied for PDT with VP at the Department of Ophthalmology, University Hospital Düsseldorf, Germany. GBM cells were applied into black-walled, glass-bottom 96-well plates and subsequently treated with VP in varying concentrations (0.001; 0.01; 0.1; 1 μM) or medium without VP for 24 h.
Concentrations	0.001; 0.01; 0.1; 1 μM
Incubation time	24 h

Animal Experiment
Animal models	Female mice
Formulation	DMSO
Dosages	6 mg/kg, 10 mg/kg, and 100 mg/kg
Administration	Intraperitoneal injection (i.p.)

Chemical Information

Molecular Weight	718.79
Formula	C41H42N4O8
CAS Number	129497-78-5
Solubility (25°C)	DMSO 50 mg/mL DMF 10 mg/mL (ultrasonic and warming)
Storage	2-8°C, protect from light

References

[1] Bailey V Fearing, et al. JOR Spine. Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

[2] Jian Chen, et al. J Cell Physiol. IL-6/YAP1/β-catenin signaling is involved in intervertebral disc degeneration

[3] Takanobu Morishita, et al. Oncotarget. The photosensitizer verteporfin has light-independent anti-leukemic activity for Ph-positive acute lymphoblastic leukemia and synergistically works with dasatinib

[4] Yi Liu-Chittenden, et al. Genes Dev. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP

[5] U Schmidt-Erfurth, et al. Surv Ophthalmol. Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration