HRO761 is a potent (IC50 = 9 nM), selective, non-covalent, and allosteric inhibitor of Werner syndrome RecQ helicase (WRN).1 It binds to the D1 and D2 helicase domain interface locking it into the inactive state. HRO761 selectively inhibits microsatellite instabile (MSI) cancer cells in vitro and in vivo via double-stranded DNA breaks, activation of the DDR, and induction of WRN degradation. It displayed synergistic effects with irinotecan in colorectal cancer cells.
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