Verteporfin
[CAS# 129497-78-5]

Identification

• Classification: API >> Special medicine >> Ophthalmic medication
• Name: Verteporfin
• Synonyms: trans-3,4-Dicarboxy-4,4a-dihydro-4a,8,14,19-tetramethyl-18-vinyl-23H,25H-benzo(b)porphine-9,13-dipropionic acid 3,4,9-trimethyl ester
• Molecular Formula: C₄₁H₄₂N₄O₈
• Molecular Weight: 718.79
• CAS Registry Number: 129497-78-5
• EC Number: 893-418-5
• SMILES: C=Cc1c(C)c2cc3nc(cc4nc(cc5[nH]c(cc1[nH]2)c(C)c5CCC(=O)O)C(CCC(=O)OC)=C4C)[C@@]1(C)C3=CC=C(C(=O)OC)[C@H]1C(=O)OC

Safety Data

• Hazard Symbols: GHS07;GHS08 Warning
• Hazard Statements: H319-H373
• Precautionary Statements: P260-P264+P265-P280-P305+P351+P338-P319-P337+P317-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

Verteporfin is a benzoporphyrin derivative used in photodynamic therapy, primarily for the treatment of age-related macular degeneration (AMD) characterized by choroidal neovascularization. It was developed to address the pathological angiogenesis in ocular diseases by exploiting its photosensitizing properties. Verteporfin becomes active upon exposure to non-thermal red light, producing reactive oxygen species that selectively damage neovascular tissues while sparing surrounding structures.

The compound was initially synthesized as part of efforts to create second-generation porphyrin-based photosensitizers with improved pharmacokinetics and reduced systemic toxicity compared to earlier agents like hematoporphyrin derivative. Verteporfin’s molecular structure allows it to bind lipoproteins in the bloodstream, which facilitates its preferential accumulation in rapidly proliferating endothelial cells of neovascular lesions. This targeting mechanism is particularly relevant in the eye, where neovascularization under the retina contributes to vision loss in wet AMD.

Upon intravenous administration, verteporfin is taken up by tissues and remains inactive until illuminated by a laser tuned to a wavelength of 689 nm. This localized activation generates singlet oxygen and other reactive species, causing oxidative damage to endothelial cells, platelet activation, and vascular occlusion. The process leads to selective closure of abnormal blood vessels without significant damage to adjacent healthy retina.

Verteporfin was approved by regulatory agencies in the early 2000s following clinical trials that demonstrated its ability to slow the progression of visual impairment in patients with predominantly classic subfoveal choroidal neovascularization. Although it does not restore lost vision, verteporfin therapy significantly reduces the risk of further vision deterioration and was a mainstay treatment before the advent of anti-VEGF (vascular endothelial growth factor) agents.

The application of verteporfin in ophthalmology also extends to other ocular disorders involving pathological neovascularization, such as pathologic myopia and presumed ocular histoplasmosis syndrome. Additionally, it has been evaluated in combination with other therapies to enhance efficacy and target different aspects of neovascular diseases.

Beyond ophthalmology, verteporfin has attracted attention in oncology research due to its potential use in photodynamic therapy for various solid tumors. Preclinical studies have demonstrated that verteporfin can accumulate in tumor vasculature and induce tumor necrosis when activated with appropriate light. Furthermore, independent of its photodynamic effects, verteporfin has shown activity as a YAP (Yes-associated protein) signaling pathway inhibitor, a mechanism that is under investigation for its relevance in cancer biology.

Despite the emergence of anti-VEGF agents that now dominate the management of wet AMD, verteporfin remains a viable alternative in certain clinical scenarios, including patients who are resistant or intolerant to other treatments. Its mechanism of action provides a complementary approach, and in some cases, combination therapy with anti-VEGF agents may be considered.

The use of verteporfin is not without limitations. Adverse effects include visual disturbances, back pain during infusion, and photosensitivity reactions, requiring patients to avoid direct sunlight or bright indoor light for at least 48 hours after treatment. Proper patient education and post-treatment care are essential to minimize these risks.

Verteporfin’s development and clinical application underscore the value of targeted photochemical approaches in medicine. Its selective activation, minimal invasiveness, and localized therapeutic effect have made it a model compound in the field of photodynamic therapy. Continued research into its molecular mechanisms and expanded indications may further enhance its clinical utility across different areas of medicine.

References

1995. Preventing intimal hyperplasia with photodynamic therapy using an intravascular probe. Annals of Vascular Surgery, 9(1).
DOI: 10.1007/bf02015320

2024. Unleashing the therapeutic power of verteporfin-eluting stents: modulating YAP signaling to combat carotid artery restenosis and cerebral watershed infarction. Molecular and Cellular Biochemistry.
DOI: 10.1007/s11010-024-05160-4

2024. Photodynamic Therapy: Advancement in Therapeutic and Cosmetic Application for Targeted Treatment: A Review. Biomedical Materials & Devices.
DOI: 10.1007/s44174-024-00248-3