Evaluation of the skin phototoxicity of systemically administered pharmaceuticals in Sprague–Dawley rats

Kim, Young Ho; Youn, Nam Hee; Yi, Jung-Sun; Kim, Joo Hwan; Cho, Yejin; Nam, Ki Taek; Park, Ki‐Sook; Lee, Jong Kwon

doi:10.1007/s43188-020-00078-7

Cited by 3 publications

(3 citation statements)

References 23 publications

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“…139,140 Most phototoxic reactions are caused by UVA; in this context, photochemistry has also been uses to perform in vitro and in vivo photosafety assessments to investigate possible adverse effects. 141,142 Photochemistry has emerged as an important tool in the field of metabolite generation and photosafety assessment. Its ability to rapidly synthesize structurally diverse metabolites and to assess the potential phototoxicity of compounds and their metabolites has enabled medicinal chemists to identify and mitigate potential safety issues early in the drug development process.…”

Section: Stereochemistry and Isomerizationmentioning

confidence: 99%

“…On the other hand, phototoxicity, defined as an acute photoinduced skin irritation, occurs when photoreactive chemicals are applied topically or systemically . Upon irradiation with sunlight, the absorbed light energy causes a molecular change in the photoreactive chemical substances, thus resulting in phototoxicity. , Most phototoxic reactions are caused by UVA; in this context, photochemistry has also been uses to perform in vitro and in vivo photosafety assessments to investigate possible adverse effects. , …”

Section: Hit-to-lead and Lead Optimizationmentioning

confidence: 99%

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Photochemistry in Medicinal Chemistry and Chemical Biology

Zhu,

Empel,

Pelliccia

et al. 2024

J. Med. Chem.

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Photochemistry has emerged as a transformative force in organic chemistry, significantly expanding the chemical space accessible for medicinal chemistry. Light-induced reactions enable the efficient synthesis of intricate organic structures and have found applications throughout the different stages of the drug discovery and development processes. Moreover, photochemical techniques provide innovative solutions in chemical biology, allowing precise spatiotemporal drug activation and targeted delivery. In this Perspective, we highlight the already numerous remarkable applications and the even more promising future of photochemistry in medicinal chemistry and chemical biology. ■ SIGNIFICANCE• Medicinal chemistry and chemical biology can highly benefit from the recent developments in the field of photochemistry in organic synthesis. • The most relevant applications of photochemistry and photocatalysis in the different stages of the drug discovery process have been highlighted. • With this Perspective, we would like to point out the potential and challenges of photochemistry in chemical biology applications.

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Section: Stereochemistry and Isomerizationmentioning

confidence: 99%

Section: Hit-to-lead and Lead Optimizationmentioning

confidence: 99%

Photochemistry in Medicinal Chemistry and Chemical Biology

Zhu,

Empel,

Pelliccia

et al. 2024

J. Med. Chem.

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“…Various in vivo models have used mice, rats and guinea pigs for phototoxicity testing. [4][5][6][7] In vitro assays, such as the 3T3 Neutral Red Uptake phototoxicity assay (3T3 NRU PT assay; OECD TG 432) and the phototoxicity test with reconstructed human epidermis (RhE Phototoxicity Test (RhE PT); OECD TG 498), have been introduced as alternative methods for phototoxicity testing. Since the publication of the ICH S10 guideline on the photosafety assessment of pharmaceuticals, 8 by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the interest in photosafety assessment has further increased as part of the pharmaceutical development process.…”

Section: Introductionmentioning

confidence: 99%

In Silico Phototoxicity Prediction of Drugs and Chemicals by using Derek Nexus and QSAR Toolbox

Ahuja,

Adiga Perdur,

et al. 2024

Altern Lab Anim

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Phototoxicity testing is crucial for evaluating the potential harmful effects of pharmaceuticals and chemicals on human skin when exposed to sunlight. Traditional in vivo models involving mice, rats, guinea pigs, as well as in vitro assays such as the 3T3 Neutral Red Uptake phototoxicity assay and methods based on the use of reconstructed human epidermis, have been established for phototoxicity testing. While these approaches are extremely valuable, they are costly in terms of both time and resources. Consequently, in silico approaches based on the use of predictive software tools can offer more rapid and cost-effective phototoxicity screening solutions. With this goal in mind, the current study evaluated two in silico tools — Derek Nexus 6.1.0/Derek Knowledge Base 2020 1.0 (Lhasa Limited, UK) and the QSAR Toolbox (v 4.5) developed by the Organisation for Economic Co-operation and Development (OECD) — for their capacity to predict the phototoxicity of several substances from diverse classes. Derek Nexus and the QSAR Toolbox were both found to be very useful for predicting the phototoxicity of drugs and other chemicals. Derek Nexus predicted phototoxicity of the compounds, with a sensitivity of 63%, specificity of 93%, Positive Predictive Values of 90% and Negative Predictive Value of 69%, overall accuracy of 77% and balanced accuracy of 78%. The QSAR Toolbox achieved sensitivity of 73%, specificity of 85%, Positive Predictive Value of 85% and Negative Predictive Value of 74%, overall accuracy of 79% and balanced accuracy of 79%. The results show that Derek Nexus and the QSAR Toolbox can be usefully incorporated in the workflow of phototoxicity testing for pharmaceuticals and chemicals.

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