GSK3685032

Research use only, not for human use.

GSK3685032 is a non-covalent and selective DNMT1 inhibitor(IC50 = 36 nM). The inhibitory effect is time-independent and reversible.

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.(In Vitro):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. 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.(In Vivo):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.

GSK-3685032 (6 days) has cell growth inhibition of majority cancer cell lines, with a median growth IC50 value of 0.64 μM.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.GSK3685032 (10-10000 nM, day 4) dose-dependently increases the immune-related gene transcription.GSK3685032 (3.2-10,000 nM, 2 days) inhibits DNMT1 protein expression.GSK3685032 induces DNA hypomethylation and gene activation. Cell Proliferation Assay Cell Line:15 leukemia, 29 lymphoma and 7 multiple myeloma cell lines, e.g., EOL-1, Ki-JK, MM.IR cells.Concentration:0.01-100 μM 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 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 Cell Line:MV4-11 cells Concentration:10-10000 nM Incubation Time:4 daysResult:Dose-dependent increased of CXCL11, IFI27, HLA-DQA1 and MAGEA4 following treatment of MV4-11 cells.Western Blot Analysis Cell Line:GDM-1 cells Concentration:3.2-10,000 nM Incubation Time:2 days Result:Inhibited DNMT1 protein expression

GSK-3685032 (1-45 mg/kg; subcutaneous twice daily for 28 days) inhibits tumor growth in the subcutaneous MV4-11 or SKM-1 xenograft models.Summary of mouse pharmacokinetic parameters for GSK-3685032.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)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.

GSK-3685032

Cell Cycle/DNA Damage

DNA/RNA Synthesis

Antiviral

——

——

2170137-61-6

420.53

C22H24N6OS

>98% (HPLC)

In Vitro:?DMSO : 25 mg/mL (59.45 mM)

CCc(c(C#N)c(N(CC1)CCC1N)nc1SC(C(N)=O)c2ccccc2)c1C#N

——

(-20℃)

With Ice Pack

≥ 2 years