Biological Activity
QN523 is an anticancer agent.1 It is cytotoxic to MiaPaCa-2, PANC-1, and BxPC-3 pancreatic cancer cells (IC50s = 0.11, 0.5, and 3.3 μM, respectively). QN523 (0.5 μM) induces cell cycle arrest at the S phase in MiaPaCa-2 cells. It increases levels of the endoplasmic reticulum (ER) stress markers glucose-regulated protein 78 kDa (GRP78), DNA damage inducible transcript 3 (DDIT3), activating transcription factor 3 (ATF3), and growth differentiation factor 15 (GDF15), as well as the autophagy markers WD repeat domain phosphoinositide-interacting protein 1 (WIPI1), GABAA receptor-associated protein-like 1 (GABARAPL1), and LC3-II in MiaPaCa-2 cells in a concentration-dependent manner. QN523 reduces tumor volume in a MiaPaCa-2 mouse xenograft model.
References
1.Kuang, Y., Ye, N., Kyani, A., et al.Induction of genes implicated in stress response and autophagy by a novel quinolin-8-yl-nicotinamide QN523 in pancreatic cancerJ. Med. Chem.65(8)6133-6156(2022)
