GSK-3685032 is a non-time-dependent, noncovalently, first-in-class reversible DNMT1-selective inhibitor, with an IC50 of 0.036 μM. GSK-3685032 induces robust loss of DNA methylation, transcriptional activation, and cancer cell growth inhibition.
GSK3685032 is a potent first-in-class DNMT1-selective inhibitor shown via crystallographic studies to compete with the active-site loop of DNMT1 for penetration into hemimethylated DNA between two CpG base pairs. GSK3685032 induces robust loss of DNA methylation, transcriptional activation, and cancer cell growth inhibition in vitro[1].
[1] M. Pappalardi. “Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia.” Nature cancer 2 1 (2021): 1002–1017.
