Open AccessImpact of Minor Structural Modifications on Properties of a Series of mTOR Inhibitors
Author(s) -
Gilles Ouvry,
Laurence Clary,
Loïc Tomas,
Michèle Aurelly,
Laetitia Bonnary,
Emilie Borde,
Claire BouixPeter,
L. Chantalat,
Claire Defoin-Platel,
Sophie Déret,
Mathieu Forissier,
Craig S. Harris,
T. Isabet,
Laurent Lamy,
Anne-Pascale Luzy,
Jonathan Pascau,
Catherine Soulet,
Alessandro Taddei,
Nathalie Taquet,
E. Thoreau,
Emeric Varvier,
Emmanuel Vial,
Laurent Hennequin
Publication year - 2019
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00401
Subject(s) - pi3k/akt/mtor pathway , chemistry , kinase , biochemistry , biophysics , computational biology , biology , signal transduction
Minor structural modifications-sometimes single atom changes-can have a dramatic impact on the properties of compounds. This is illustrated here on structures related to known mTOR inhibitor Sapanisertib. Subtle changes in the hinge binder lead to strikingly different overall profiles with changes in physical properties, metabolism, and kinase selectivity.