A dual inhibitor of PI3Kα and mTOR
PQR530 is a dual inhibitor of PI3Kα and mammalian target of rapamycin (mTOR; IC50s = 11.1 and 7.4 nM, respectively).1 It inhibits phosphorylation of Akt and ribosomal S6 kinase in A2058 melanoma cells (IC50s = 62.2 and 61.1 nM, respectively). PQR530 inhibits cell growth in a panel of 66 cancer cell lines (mean GI50 = 0.43 ?M). In vivo, PQR530 (25 mg/kg) reduces tumor growth in an OVCAR-3 ovarian cancer mouse xenograft model. It decreases the number of seizures per week in a Tsc1GFAP conditional knockout mouse model of epilepsy.2
1.Rageot, D., Bohnacker, T., Keles, E., et al.(S)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530, a potent, orally bioavailable and brain penetrable dual inhibitor of class I PI3K and mTOR kinaseJ. Med. Chem.62(13)6241-6261(2019) 2.Theilmann, W., Gericke, B., Schidlitzki, A., et al.Novel brain permeant mTORC1/2 inhibitors are as efficacious as rapamycin or everolimus in mouse models of acquired partial epilepsy and tuberous sclerosis complexNeuropharmacology180108297(2020)
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