GSK-3685032|cas:2170137-61-6|西域试剂

GSK-3685032,99.95%

产品编号：Bellancom-139664| CAS NO：2170137-61-6| 分子式：C₂₂H₂₄N₆OS| 分子量：420.53

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货号	价格	库存与货期
Bellancom-139664	￥3500.00	杭州北京（现货）
Bellancom-139664	￥5800.00	杭州北京（现货）
Bellancom-139664	￥11000.00	杭州北京（现货）

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GSK-3685032

产品介绍

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。

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.

体外研究

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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 days
Result:	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

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.

Summary of mouse pharmacokinetic parameters for GSK-3685032

Dose,Route	C_max (ng/mL)	AUC_0-8hr (h*ng/mL)	DNAUC (hkgng/mL/mg)	Clearance (mL/min/kg)	Volume_dss (L/kg)	T_1/2 (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

西域 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)
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.

体内研究

Dose,Route	C_max (ng/mL)	AUC_0-8hr (h*ng/mL)	DNAUC (hkgng/mL/mg)	Clearance (mL/min/kg)	Volume_dss (L/kg)	T_1/2 (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

西域 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)
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.

体内研究

Dose,Route	C_max (ng/mL)	AUC_0-8hr (h*ng/mL)	DNAUC (hkgng/mL/mg)	Clearance (mL/min/kg)	Volume_dss (L/kg)	T_1/2 (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

西域 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)
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.

性状

Solid

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。