| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| ln Vitro |
GSK-3685032 (6 days) has a median growth IC50 value of 0.64 μM, which indicates that it inhibits the development of most cancer cell lines [1]. With a decreased growth IC50 during the whole 6-day duration, GSK-3685032 (0.1-1000 nM, days 1-6) demonstrates growth inhibition after 3 days [1]. Dose-dependently, immune-related gene transcription is increased by GSK3685032 (10–1000 nM, day 4) [1]. The expression of DNMT1 protein is suppressed by GSK3685032 (3.2-10,000 nM, 2 days) [1]. DNA hypomethylation and gene activation are induced by GSK3685032 [1].
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| ln Vivo |
In subcutaneous MV4-11 or SKM-1 xenograft models, GSK-3685032 (1–45 mg/kg; subcutaneous injection twice daily for 28 days) slows the formation of tumors [1]. Mouse pharmacokinetic parameters summary: GSK-3685032[1]; dosage, route; Cmax (ng/mL); AUC0-8hr (h*ng/mL); DNAUC (h*kg*ng/mL/mg); clearance rate (mL/min/kg); volume (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
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| Cell Assay |
Cell proliferation assay [1]
Cell Types: 15 leukemia cells, 29 lymphoma cells, and 7 multiple myeloma cell lines, such as EOL-1, Ki-JK, MM.IR cells. Tested Concentrations: 0.01-100 μM Incubation Duration: 6 days Experimental Results: demonstrated cell growth inhibition on most cancer cell lines, with a median growth IC50 value of 0.64 μM. Cell proliferation assay [1] Cell Types: MV4-11 Cell Tested Concentrations: 0.1-1000 nM Incubation Duration: 1-6 days Experimental Results: Growth inhibition was demonstrated after 3 days, and the growth IC50 gradually diminished during the entire 6 d time course. RT-PCR[1] Cell Types: MV4-11 Cell Tested Concentrations: 10-10000 nM Incubation Duration: 4 days Experimental Results: CXCL11, IFI27, HLA-DQA1 and MAGEA4 increased in a dose-dependent manner after MV4-11 cell treatment. Western Blot Analysis[1] Cell Types: GDM-1 Cell Tested Concentrations: 3.2-10,000 nM Incubation Duration: 2 days Experimental Results: DNMT1 protein expression was inhibited |
| Animal Protocol |
Animal/Disease Models: MV4-11 xenograft model (female CD1-Foxn1 mice, 12 weeks old) or SKM-1 xenograft model (NOD.CB17-Prkdc1NCrCrl mice, 8-11 weeks old) [1]
Doses: 1, 5, 15, 30, 45 mg/kg (10% Captisol adjusted to pH 4.5-5 with 1 M acetic acid, store at 4 °C for up to 1 week) Route of Administration: SC, twice (two times) daily, continuous 4-week Experimental Results: Demonstrated statistically significant dose-dependent tumor growth inhibition, with significant regression at ≥30 mg/kg. |
| 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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| Molecular Formula |
C22H24N6OS
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|---|---|
| Molecular Weight |
420.54
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| CAS # |
2170137-61-6
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| Related CAS # |
(R)-GSK-3685032;2170140-50-6;(S)-GSK-3685032;2170142-58-0
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C(N)C(SC1=NC(N2CCC(N)CC2)=C(C#N)C(CC)=C1C#N)C3=CC=CC=C3
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| InChi Key |
KNKHRZYILDZLRE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24N6OS/c1-2-16-17(12-23)21(28-10-8-15(25)9-11-28)27-22(18(16)13-24)30-19(20(26)29)14-6-4-3-5-7-14/h3-7,15,19H,2,8-11,25H2,1H3,(H2,26,29)
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| Chemical Name |
2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl)thio)-2-phenylacetamide
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| Synonyms |
GSK3685032 GSK-3685032 GSK 3685032
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~59.45 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.94 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3779 mL | 11.8895 mL | 23.7790 mL | |
| 5 mM | 0.4756 mL | 2.3779 mL | 4.7558 mL | |
| 10 mM | 0.2378 mL | 1.1889 mL | 2.3779 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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