Skin Partitioning Prediction of Drug-like Compounds

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F15%3A33156088" target="_blank" >RIV/61989592:15310/15:33156088 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Skin Partitioning Prediction of Drug-like Compounds

Original language description

Here we report the developments on in silico methods usable for prediction of partitioning into skin lipids. We have developed simple bilayer models of ceramides or skin lipid mixture. Using continuum solvent method - COSMOmic, we have evaluated free energy profiles of individual drug-like compounds and we concluded that skin lipid mixture model is more reliable to predict partitioning of set of 20 compounds into skin lipids when compared to experimentally measured values. We have also assessed the effect of conformers and ionizable groups. Finally, we have also studied possibilities of advanced sampling method for molecular dynamics of skin barrier membrane - metadynamics - in order to generate free energy profiles for comparison. This methodology isintended to add piece for calculation of bioavailability of permeants via skin absorption in collaboration with P&G.

Czech name

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Czech description

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Type

V_souhrn - Summary research report

CEP classification

CF - Physical chemistry and theoretical chemistry

OECD FORD branch

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Project

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Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2015

Confidentiality

C - Předmět řešení projektu podléhá obchodnímu tajemství (§ 504 Občanského zákoníku), ale název projektu, cíle projektu a u ukončeného nebo zastaveného projektu zhodnocení výsledku řešení projektu (údaje P03, P04, P15, P19, P29, PN8) dodané do CEP, jsou upraveny tak, aby byly zveřejnitelné.

Number of pages

36

Place of publication

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Publisher/client name

Procter&amp;Gamble

Version

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