R-268712|cas:879487-87-3|西域试剂

R-268712,99.78%

产品编号：Bellancom-12953| CAS NO：879487-87-3| 分子式：C₂₀H₁₈FN₅O| 分子量：363.39

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货号	价格	库存与货期
Bellancom-12953	￥930.00	杭州北京（现货）
Bellancom-12953	￥1400.00	杭州北京（现货）
Bellancom-12953	￥2100.00	杭州北京（现货）
Bellancom-12953	￥8500.00	杭州北京（现货）
Bellancom-12953	￥0.00	杭州北京（现货）

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R-268712

产品介绍

R-268712 是一种口服有效的选择性 ALK-5 抑制剂，其 IC₅₀ 值为 2.5 nM。R-268712 能以剂量依赖的方式抑制 Smad3 的磷酸化，其 IC₅₀ 值为 10.4 nM。R-268712 通过抑制TGF-β 的信号传导来抑制肾小球肾炎以及肾小球硬化，可用于肾脏纤维化和癌症的研究。

生物活性

R-268712 is an orally active and selective ALK-5 inhibitor, with an IC₅₀ of 2.5 nM. R-268712 inhibits the phosphorylation of Smad3 in a dose-dependent manner with an IC₅₀ of 10.4 nM. R-268712 suppresses glomerulonephritis as well as glomerulosclerosis by inhibiting TGF-β signaling, which can be used in studies of renal fibrosis and cancer.

体外研究

R-268712 (3, 10, 30, 100, 300 nM; 1 h) inhibits the phosphorylation of Smad3 in a dose-dependent manner with an IC₅₀ of 10.4 nM in HFL-1 cells. R-268712 (3, 10, 30, 100, 300 nM; 72 h) inhibits myofibroblast transdifferentiation (MTD) from fibroblasts in a dose-dependent manner without inhibition of cell growth in HFL-1cells.

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

Cell Viability Assay

Cell Line:	HFL-1 cells
Concentration:	3, 10, 30, 100, 300 nM
Incubation Time:	1 or 72 h
Result:	Inhibited the phosphorylation of Smad3 in a dose-dependent manner with an IC₅₀ of 10.4 nM when incubation 1 h. Suppressed myofibroblast transdifferentiation (MTD) from fibroblasts in a dose-dependent manner without inhibition of cell growth when incubation after 72 h.

体内研究
(In Vivo)

R-268712 (0.3, 1, 3, 10 mg/kg; p.o.; single) shows AUC_0-24 values of 0.075, 0.28, 1.6 and 8.2 μg•h/mL for dosages of 0.3, 1, 3, 10 mg/kg, respectively.
R-268712 (1, 3, 10 mg/kg; p.o.; single daily for 3 days) inhibits renal luciferase activity in a dose-dependent manner in UUO model.
R-268712 (0.3, 1 mg/kg; p.o.; single daily for 33 days) shows renoprotective effects (improves and maintains renal function as well as inhibits glomerular sclerosis) on Thy1 nephritis model when at dosage of 1 mg/kg.

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

Animal Model:

Male WKY/Hos rats.

Dosage:

0.3, 1, 3, and 10 mg/kg

Administration:

Oral administration; single.

Result:

1.19 Pharmacokinetic Parameters of R-268712 in male WKY/Hos rats (n=4).

	PO (0.3 mg/kg)	PO (1 mg/kg)	PO (3 mg/kg)	PO (10 mg/kg)
AUC_0-24 (µg•h/mL)	0.075	0.28	1.6	8.2

Animal Model:	Male Col1a1-Luc Tg rats (10 to14-week-old; UUO model; n=5-6).
Dosage:	1, 3, 10 mg/kg
Administration:	Oral administration; single daily for 3 days.
Result:	Suppressed activity of renal luciferase in a dose-dependent manner.

Animal Model:	Male WKY/Hos rats (4-week-old; Thy1 nephritis model; n=7).
Dosage:	0.3, 1 mg/kg
Administration:	Oral administration; single daily for 33 days.
Result:	Significantly reduced proteinuria at day 21( the repression continued until day 28), and serum creatinine level (dosage at 1 mg/kg). Apparently suppressed glomerular sclerosis by 28% and reduced the increase of the hydroxyproline content when at 1 mg/kg. Suppressed the activation of mesangial parenchymal cell and the injury of podocyte on the basis of TGF-β signaling inhibition at 1 mg/kg.

体内研究

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

Animal Model:

Male WKY/Hos rats.

Dosage:

0.3, 1, 3, and 10 mg/kg

Administration:

Oral administration; single.

Result:

1.19 Pharmacokinetic Parameters of R-268712 in male WKY/Hos rats (n=4).

	PO (0.3 mg/kg)	PO (1 mg/kg)	PO (3 mg/kg)	PO (10 mg/kg)
AUC_0-24 (µg•h/mL)	0.075	0.28	1.6	8.2

Animal Model:	Male Col1a1-Luc Tg rats (10 to14-week-old; UUO model; n=5-6).
Dosage:	1, 3, 10 mg/kg
Administration:	Oral administration; single daily for 3 days.
Result:	Suppressed activity of renal luciferase in a dose-dependent manner.

Animal Model:	Male WKY/Hos rats (4-week-old; Thy1 nephritis model; n=7).
Dosage:	0.3, 1 mg/kg
Administration:	Oral administration; single daily for 33 days.
Result:	Significantly reduced proteinuria at day 21( the repression continued until day 28), and serum creatinine level (dosage at 1 mg/kg). Apparently suppressed glomerular sclerosis by 28% and reduced the increase of the hydroxyproline content when at 1 mg/kg. Suppressed the activation of mesangial parenchymal cell and the injury of podocyte on the basis of TGF-β signaling inhibition at 1 mg/kg.

体内研究

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

Animal Model:

Male WKY/Hos rats.

Dosage:

0.3, 1, 3, and 10 mg/kg

Administration:

Oral administration; single.

Result:

1.19 Pharmacokinetic Parameters of R-268712 in male WKY/Hos rats (n=4).

	PO (0.3 mg/kg)	PO (1 mg/kg)	PO (3 mg/kg)	PO (10 mg/kg)
AUC_0-24 (µg•h/mL)	0.075	0.28	1.6	8.2

Animal Model:	Male Col1a1-Luc Tg rats (10 to14-week-old; UUO model; n=5-6).
Dosage:	1, 3, 10 mg/kg
Administration:	Oral administration; single daily for 3 days.
Result:	Suppressed activity of renal luciferase in a dose-dependent manner.

Animal Model:	Male WKY/Hos rats (4-week-old; Thy1 nephritis model; n=7).
Dosage:	0.3, 1 mg/kg
Administration:	Oral administration; single daily for 33 days.
Result:	Significantly reduced proteinuria at day 21( the repression continued until day 28), and serum creatinine level (dosage at 1 mg/kg). Apparently suppressed glomerular sclerosis by 28% and reduced the increase of the hydroxyproline content when at 1 mg/kg. Suppressed the activation of mesangial parenchymal cell and the injury of podocyte on the basis of TGF-β signaling inhibition at 1 mg/kg.

性状

Solid

溶解性数据

In Vitro:

DMSO : 125 mg/mL (343.98 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.7519 mL	13.7593 mL	27.5186 mL
5 mM	0.5504 mL	2.7519 mL	5.5037 mL
10 mM	0.2752 mL	1.3759 mL	2.7519 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: ≥ 2.08 mg/mL (5.72 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (5.72 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (5.72 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (5.72 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (5.72 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (5.72 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。