Abstract information for the 2013 ICCP450 Meeting
SUBMISSIONS ARE NOW CLOSED
- Poster boards (max poster size – 44 in x 40 in; 1.1 x 1.0 m2) will be located in our conference venue near the lecture halls and refreshment break areas.
- Please note that at least one author must register and attend the conference to present the poster (or platform presentation).
- Several poster submissions may be selected for oral presentations in the symposia.
Instructions for Preparation of your Abstract
- Write in English using the Times New Roman font, 12 pt capitals for the title, 11 pt for the authors’ names, 11 pt for institutional addresses and 11 pt for the abstract text.
- One page, 400 word maximum, text right justified.
- Underline the presenting author and include his/her email address.
- Page margins should be 1 inch or 2.5 cm on the top, left and right. The bottom margin should be at least 1 inch or 2.5 cm. Please block justify the text.
- Prepare both Word and PDF files for submission.
- Please adhere to the template below in order to ensure the correct formatting of your abstract.
HYDANTOIN AND BARBITURATE INHIBITORS OF CYP2C19 AND CYP2C9
Consideration of the relative affinities of CYP2C9 and CYP2C19 for phenytoin and mephenytoin suggests that alkylation at the N-3 position on the hydantoin ring is an important determinant of isoform selectivity. Therefore, in order to refine our existing CoMFA model for CYP2C9 (Jones et al., DMD 24:1, 1996) and permit construction of a new model for CYP2C19, we synthesised three series of N-3 substituted phenytoin, nirvanol and phenobarbital derivatives and determined their Ki values against recombinant CYP2C9 and CYP2C19. Enantiomers in the phenobarbital and nirvanol series were resolved such that the inhibitory potencies of a total of 24 compounds were evaluated with each isoform. (S)-Flurbiprofen 4'-hydroxylation and 3-O-methylfluorescein O-demethylation served as highly sensitive fluorescent reporter HPLC assays for reconstituted CYP2C9 and CYP2C19, respectively. Almost all the N-3 alkyl substituted compounds were found to be competitive inhibitors of both isoforms, although the degree of inhibition was always much greater for CYP2C19. Inhibition was also pronouncedly stereoselective for CYP2C19, but not CYP2C9. (R)-3-Benzyl-phenobarbital emerged as the most potent inhibitor in the series with a Ki towards CYP2C19 of 80 nM. The construction of new CoMFA models for CYP2C9 and CYP2C19 based on these data is now in progress.
- Go to https://cmt.research.microsoft.com/ICC2013/.
- Title – please provide your abstract title here for indexing purposes.
- Abstract box - Paste Word version of your abstract here.
- Authors – click Add Author button and insert email address/affiliation etc. for all authors.
- Subject areas – please select a primary and secondary subject area.
- File upload – please upload a PDF of your abstract here. This is the version that will be reviewed.
- Additional question – please select the best description of your occupation/position; faculty, student etc.
- Hit the Submit button.