GSK3685032 is a non-covalent and selective DNMT1 inhibitor(IC50 = 36 nM). The inhibitory effect is time-independent and reversible. GSK3685032 induces loss of DNA methylation and transcriptional activation and inhibits cancer cell growth.

MM.IR cells:0.64 μM, EOL-1 cells:0.64 μM, Ki-JK cells:0.64 μM, DNMT1:36 nM

In MV4-11 cells, GSK3685032 (0.1-1000 nM, 1-6 days) exhibited growth inhibition after 3 days, with decreasing growth IC50 throughout a 6 d time course. GSK3685032 (10-10000 nM, day 4) increased the immune-related gene transcription in a dose dependent manner[1]. GSK3685032 (3.2-10,000 nM, 2 days) inhibited DNMT1 protein expression. In 15 leukemia, 29 lymphoma and 7 multiple myeloma cell lines, e.g., EOL-1, Ki-JK, MM.IR cells, GSK3685032 (6 days) showed cell growth inhibition of majority cancer cell lines, with a median growth IC50 value of 0.64 μM. GSK3685032 induced DNA hypomethylation and gene activation[1].

In MV4-11 xenograft models or SKM-1 xenograft models, GSK-3685032 (1-45 mg/kg; s.c.) inhibited dose-dependent tumor growth with clear regression at ≥30 mg/kg[1].