| Identification | Back Directory | [Name]
Benzeneacetamide, α-[[6-(4-amino-1-piperidinyl)-3,5-dicyano-4-ethyl-2-pyridinyl]thio]- | [CAS]
2170137-61-6 | [Synonyms]
Benzeneacetamide, α-[[6-(4-amino-1-piperidinyl)-3,5-dicyano-4-ethyl-2-pyridinyl]thio]- | [Molecular Formula]
C22H24N6OS | [MOL File]
2170137-61-6.mol | [Molecular Weight]
420.54 |
| Chemical Properties | Back Directory | [Boiling point ]
669.4±55.0 °C(Predicted) | [density ]
1.33±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 25 mg/mL (59.45 mM; Need ultrasonic) | [form ]
Solid | [pka]
14.65±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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[1]. | [Biological Activity]
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[1].
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[1].GSK3685032 induces DNA hypomethylation and gene activation[1].
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[1]. Summary of mouse pharmacokinetic parameters for GSK-3685032[1] Dose,Route Cmax(ng/mL) AUC0-8hr(h*ng/mL) DNAUC(h*kg*ng/mL/mg) Clearance(mL/min/kg) Volumedss(L/kg) T1/2(h) 2 mg/kg,IV 5103 2418 1209 13 1.3 1.8 2 mg/kg,SC 252 921 461 NA NA 2.8 2 mg/kg,SC 5473 15400 513 NA NA ND | [in vivo]
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[1].
Summary of mouse pharmacokinetic parameters for GSK-3685032[1]
| Dose,Route | Cmax
(ng/mL) | AUC0-8hr
(h*ng/mL) | DNAUC
(h*kg*ng/mL/mg) | Clearance
(mL/min/kg) | Volumedss
(L/kg) | T1/2
(h) | | 2 mg/kg,IV | 5103 | 2418 | 1209 | 13 | 1.3 | 1.8 | | 2 mg/kg,SC | 252 | 921 | 461 | NA | NA | 2.8 | | 2 mg/kg,SC | 5473 | 15400 | 513 | NA | NA | ND |
| 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. |
| [storage]
Store at -20°C | [References]
[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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DC Chemicals
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