GSK-3685032

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GSK-3685032  纯度: 98.53%

GSK-3685032 是一种非时间依赖、非共价、可逆的 DNMT1 选择性抑制剂，IC50=0.036 μM。GSK-3685032 诱导 DNA 甲基化丧失、转录激活和癌细胞生长抑制。

GSK-3685032

GSK-3685032 Chemical Structure

CAS No. : 2170137-61-6

规格 价格 是否有货 数量
5 mg ￥3500 In-stock
10 mg ￥5800 In-stock
25 mg ￥11000 In-stock
50 mg   询价  
100 mg   询价  

* Please select Quantity before adding items.

GSK-3685032 相关产品

•相关化合物库:

  • Bioactive Compound Library Plus
  • Epigenetics Compound Library
  • Anti-Cancer Compound Library
  • Reprogramming Compound Library
  • Anti-Blood Cancer Compound Library
  • Transcription Factor Targeted Library

生物活性

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].

IC50 & Target

DNMT1[1]
体外研究
(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[1].
GSK3685032 induces DNA hypomethylation and gene activation[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[1]

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[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

体内研究
(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

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

分子量

420.53

Formula

C22H24N6OS
CAS 号

2170137-61-6
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 25 mg/mL (59.45 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.3780 mL 11.8898 mL 23.7795 mL
5 mM 0.4756 mL 2.3780 mL 4.7559 mL
10 mM 0.2378 mL 1.1890 mL 2.3780 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (5.94 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.94 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (5.94 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.94 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (5.94 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.94 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [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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