Synthetic lethality represents a promising strategy to enhance cancer cell sensitivity to chemotherapy agents. This occurs when the simultaneous mutation or inactivation of two genes induces cell death, whereas mutation of either gene alone has no impact on cell survival. Identifying similar synthetic lethal gene pairs in tumor cells offers significant potential for precisely targeting cancer cells. Recently, WRN helicase has emerged as a prominent synthetic lethal target in tumors characterized by microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR).

On April 24, 2024, Novartis published papers in Nature titled "Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers," detailing their recent progress in developing drugs that exploit synthetic lethality by targeting WRN helicase. At Abovchem, we offer a wide range of building blocks for HRO761 and its SAR studies.