2244904-70-7

6,7-Dimethoxy-2-methyl-N-[(1R)-1-[4-[2-[(methylamino)methyl]phenyl]-2-thienyl]ethyl]-4-quinazolinamine is an effective and selective inhibitor of SOS1, blocking RAS activation via disruption of the KRAS-SOS1 interaction without significantly targeting the EGFR receptor. Thus, it has potential use in treatment of hyperproliferative disorders.

BAY-293 selectively inhibits SOS1-mediated KRAS activation (IC50 = 52 nM; 50 nM wt or G12C hKRAS & 10 nM SOS1cat) via direct SOS1 bindingblocking SOS1-KRAS interaction (IC50 = 21 nM; 10 nM hSOS1c at & 5 nM hKRAS G12C) without affecting (IC50 >20 μM) CRAF RBD-KRAS interactionKRAS G12C activation by SOS2Cdc42 activation by DBSor EGFR kinase activity. BAY-293 downregulates cellular active RAS (IC50 = 200 nM/Calu-1410 nM/HeLa) and downstream ERK phosphorylation (K-562150 nM/Calu-1) with good target selectivity as assessed over 358 kinases (<37% inhibition at 1 μM) and a panel of 77 GPCRstransportersnuclear receptors and enzymes.

KRAS-SOS1: 21 nM (IC₅₀)

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