Marie-Hélène Larraufie, PhD
(Co-Mentor: Jeremy Jenkins, PhD)
Chemical Biology & Therapeutics
Cambridge, Massachusetts, United States
Selective tissue targeting is emerging as a powerful approach for minimizing adverse effects, augmenting efficacy, and extending indication opportunities of pharmacological agents. Among the different tissue-targeting modalities available, we are particularly interested in the targeted-prodrug approach, where the drug is specifically released in the cell-type or tissue of interest after chemical modification of the parent, as it offers potential for exquisite selectivity while retaining the desirable drug-like properties of small molecules. We believe that the emergence of extensive tissue-based transcriptional profiling data presents a unique opportunity for the prodrug field, by enabling the identification of tissue-specific enzymes and metabolic reactions. We are interested in the development of a novel strategy to leverage tissue-based transcriptional profiling data for the rational design of tissue-selective prodrugs using a combination of bio/chem informatics analysis, in silico screening, and new biochemical and phenotypic screening formats specifically adapted to prodrugs.
Incorporation of metabolically stable ketones into a small molecule probe to increase potency and water solubility.
Larraufie MH, Yang WS, Jiang E, Thomas AG, Slusher BS, Stockwell BR.
Bioorg Med Chem Lett. 2015 Nov 1;25(21):4787-92.
Radical migration of substituents of aryl groups on quinazolinones derived from N-acyl cyanamides.
Larraufie MH, Courillon C, Ollivier C, Lacôte E, Malacria M, Fensterbank L.
J Am Chem Soc. 2010 Mar 31;132(12):4381-7.
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