| Description |
GSK-3685032 is a non-time-dependent, noncovalently, first-in-class reversible DNMT1-selective inhibitor, whit an IC50 of 0.036 μM. GSK-3685032 induces robust loss of DNA methylation, transcriptional activation and cancer cell growth inhibition[1].
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| Related Catalog |
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| In Vitro |
GSK-3685032 (6 days) has cell growth inhibition of majority cancer cell lines, with a median growth IC50 value of 0.64 μM[1]. GSK-3685032 (0.1-1000 nM, 1-6 days) exhibits growth inhibition after 3 days, with decreasing growth IC50 throughout a 6 d time course[1]. GSK3685032 (10-10000 nM, day 4) dose-dependently increases the immune-related gene transcription[1]. GSK3685032 (3.2–10,000 nM, 2 days) inhibits DNMT1 protein expression. GSK3685032 induces DNA hypomethylation and gene activation[1]. Cell Proliferation Assay[1] Cell Line: 15 leukemia, 29 lymphoma and 7 multiple myeloma cell lines Concentration: 0.01-100μM Incubation Time: 6 days Result: Showed cell growth inhibition of majority cancer cell lines, with a median growth IC50 value of 0.64 μM. Cell Proliferation Assay[1] Cell Line: MV4–11 cells Concentration: 0.1-1000 nM Incubation Time: 1-6 days Result: Exhibited growth inhibition after 3 days, with decreasing growth IC50 throughout a 6 d time course. RT-PCR[1] Cell Line: MV4–11 cells Concentration: 10-10000 nM Incubation Time: 4 days Result: Dose-dependent increased of CXCL11, IFI27, HLA-DQA1 and MAGEA4 following treatment of MV4–11 cells. Western Blot Analysis[1] Cell Line: GDM-1 cells Concentration: 3.2-10,000 nM Incubation Time: 2 days Result: Inhibited DNMT1 protein expression
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| In Vivo |
GSK3685032 (1-45 mg/kg, subcutaneous, twice daily, 0-28 days) inhibits tumor growth in the subcutaneous MV4–11 or SKM-1 xenograft models[1]. Animal Model: MV4–11 xenograft models(female CD1-Foxn1 mice, 12 weeks of age) or SKM-1 xenograft models (NOD. CB17-Prkdc1NCrCrl mice, 8–11 weeks of age )[1] Dosage: 1, 5, 15, 30,45 mg/kg (10% captisol adjusted to pH 4.5-5 with 1 M acetic acid）,stored for up to 1 week at 4 °C) Administration: Subcutaneous injection, twice daily for 4 weeks Result: Revealed statistically significant dose-dependent tumor growth inhibition with clear regression at ≥30 mg/kg.
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| References |
[1]. [1] Pappalardi MB, et al. Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nat Cancer. 2021;2(10):1002-1017.
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