Journal ArticleDOI
Can light absorption and photostability data be used to assess the photosafety risks in patients for a new drug molecule
TLDR
The current study was undertaken to determine the level of light absorption by measuring the molar extinction coefficients (MEC) of a wide range of compounds reported in the literature to have known photosafety issues in humans and the results have shown that all compounds tested have absorbance intensities significantly above an MEC threshold of 1000 L mol (-1)cm(-1) and also display a widerange of photoinstability.Abstract:
Photosafety assessments are recommended for all new drug candidates intended for clinical use. In 2002, Testing guidances were issued by the regulatory authorities in the USA (2003) and Europe (2002). A key requirement is to measure the absorption of UV-visible light by a compound in the 290-700 nm range and to assess photostability. Further photosafety evaluation is recommended for molecules which absorb light energy in this region and may be unstable in light. Consequently, the current guidances do not specify what constitutes a significant level of light absorbance or photoinstability. The current study was undertaken to determine the level of light absorption by measuring the molar extinction coefficients (MEC) of a wide range of compounds reported in the literature to have known photosafety issues in humans. The results have shown that all compounds tested have absorbance intensities significantly above an MEC threshold of 1000 L mol(-1)cm(-1) and also display a wide range of photoinstability. The measurement of light absorption is a contributing part of an overall pre-clinical photosafety risk assessment process, whereas photostability assessments have proven to have limited value. Molecules with an MEC less than 1000 L mol(-1)cm(-1)are deemed less of a photosafety risk since this low level of light absorption is unlikely to prove harmful.read more
Citations
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Journal ArticleDOI
Criteria for the Research Institute for Fragrance Materials, Inc. (RIFM) safety evaluation process for fragrance ingredients
A.M. Api,D. Belsito,Magnus Bruze,Peter A. Cadby,Peter Calow,Maria Lúcia Zaidan Dagli,W. Dekant,Graham Ellis,Allison D. Fryer,M. Fukayama,Peter Griem,C. Hickey,L Kromidas,J F Lalko,Daniel C. Liebler,Yoshiki Miyachi,Valerie T. Politano,Kevin J. Renskers,G. Ritacco,D. Salvito,Terry W Schultz,I. G. Sipes,B. Smith,D. Vitale,D K Wilcox +24 more
TL;DR: This publication is designed to update the RifM safety assessment process, which follows a series of decision trees, reflecting advances in approaches in risk assessment and new and classical toxicological methodologies employed by RIFM over the past ten years.
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Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1
Robert L. Dow,Jian-Cheng Li,Michael Patrick Pence,E. Michael Gibbs,Jennifer L. LaPerle,John Litchfield,David W. Piotrowski,Michael John Munchhof,Tara B. Manion,William J. Zavadoski,Gregory S. Walker,R. Kirk McPherson,Susan Tapley,Eliot Sugarman,Angel Guzman-Perez,Paul DaSilva-Jardine +15 more
TL;DR: Compound 3 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points and has been advanced to human clinical studies.
Book ChapterDOI
Designing Drugs to Avoid Toxicity
TL;DR: Good medicinal chemistry design, taking into account both potency at the target and also the predictive toxicology discussed in this chapter, increases the probability of a project's success and heavily influences speed of reaching a clear proof of concept outcome.
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Studies on photodegradation process of psychotropic drugs: a review
Jakub Trawiński,Robert Skibiński +1 more
TL;DR: An overview on photolytic as well as homogenous and heterogeneous photocatalytic degradation methods with the use of various catalysts is presented andsembling of MS/MS spectra libraries of drug molecules and their phototransformation products was identified as the future challenge.
References
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QSPR: the correlation and quantitative prediction of chemical and physical properties from structure
Book
The Science of Photobiology
TL;DR: The scientific program of the first meeting of the American Society for Photobiology included discussions of the detrimental effects of excessive exposure to sunlight and artificial uv radiation and repair of uv-induced damage to cells.
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Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management.
TL;DR: Some recent studies suggest that diet supplementation with antioxidants may be beneficial in increasing the minimum erythemal UV radiation dose and prevention of photosensitivity involves adequate protection from the sun with clothing and sunscreens.
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Ultraviolet-Visible Spectrophotometry in Pharmaceutical Analysis
TL;DR: Measurement of light absorption correlation between the structures and spectra of drug substances spectrophotometric methods based on chemical reactions spectrophOTometric analysis of some important groups of drug substance.
Journal ArticleDOI
Analytical Studies on the Prediction of Photosensitive/Phototoxic Potential of Pharmaceutical Substances
Satomi Onoue,Yoshiko Tsuda +1 more
TL;DR: Results indicated that known photosensitive/phototoxic compounds tested have the ability to generate ROS under light exposure, and this photochemical reaction could be associated with their photoinstability and/or phototoxic responses.
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