PQR620

PQR620 is a brain-penetrant, ATP-competitive, potent and selective mTORC1/2 inhibitor with >3700-fold lower potency toward class class I/III PI3K isoforms (mTOR Kd = 0.27 nM, p110α/β/δ/γ Kd = 1/22/23/18 µM, VPS34 Kd = 27.5 µM) and PI4Kβ (Kd >30 µM). PQR620 effectively inhibits cellular mTOR substrates phosphorylation (IC50 = 190 nM/Akt pS473 and 85.2 nM/S6 pS235/236 in A2058 cells) and exhibits antiproliferation activity in cancer cultures (mean GI50 post 72h = 0.92 µM among 66 cancer lines). PQR620 suppresses human ovarian cancer OVCAR-3 tumor growth in mice (50 mg/kg/d p.o.) and eliminates seizure activity of Tsc1GFAP conditional knockout mice in vivo (100 mg/kg/d p.o.).