Inhibitors of thapsigargin-induced cell death

Details Inhibitors of thapsigargin-induced cell death Inhibitors of thapsigargin-induced cell death

A - Human Necessities

61

K

A61K 31/5513 (2006.01) A61K 31/395 (2006.01) A61K 31/495 (2006.01) A61K 31/496 (2006.01) C07D 209/86 (2006.01) C07D 243/38 (2006.01) C07D 295/12 (2006.01) C12M 1/34 (2006.01) C12Q 1/02 (2006.01) C40B 30/06 (2006.01) C12Q 1/18 (2006.01)

Patent

CA 2687187

Methods for screening for inhibitors of endoplasmic reticulum (ER) stress are provided. These methods involve the addition of thapsigargin, which induces ER stress, and a test agent to mammalian cells in multi-well plates. Cell survival can be readily monitored by measuring intracellular ATP content using a bioluminescent reagent. Screening a commercially available library of 50,000 compounds led to the identification of 93 hit compounds that were subjected to secondary assays to confirm their ability to rescue cells from thapsigargin-induced cell death.

L'invention concerne des procédés de criblage d'inhibiteurs de stress du réticulum endoplasmique (ER). Ces procédés impliquent l'addition de thapsigargine, qui induit le stress ER, et un agent d'essai destiné à des cellules de mammifères dans des plaques multipuits. La survie des cellules peut être aisément contrôlée par mesure du contenu intracellulaire ATP au moyen d'un réactif bioluminescent. Le criblage d'une bibliothèque de 50'000 composés commercialement disponibles conduit à l'identification de 93 composés têtes de série qui ont été soumis à des dosages secondaires afin de confirmer leur capacité à sauver les cellules de la mort cellulaire induite par la thapsigargine.

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