SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC₅₀ of 48 nM, and > 100-fold selectivity over TGF-βRII.

IC50: 48 nM (TGF-βRI)

SD-208 inhibits the cell growth and constitutive and TGF-beta-evoked migration and invasion, and enhances immunogenicity in murine SMA-560 and human LN-308 glioma cells^[1]. SD-208 blocks TGF-beta-induced phosphorylation of the receptor-associated Smads, Smad2 and Smad3, and stimulates epithelial-to-mesenchymal transdifferentiation, migration, and invasiveness into Matrigel in vitro^[2]. SD-208 also abolishes the promoting effect of TGF-β on neointimal smooth muscle-like cell (SMLC) proliferation and migration in vitro^[3].

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.

SD-208 (1 mg/mL, p.o.) significantly prolongs the median survival of SMA-560 glioma-bearing mice^[1]. In syngeneic 129S1 mice, SD-208 (60 mg/kg/d, p.o.) inhibits primary R3T tumor growth, and reduces the number and the size of lung metastases^[2]. In the murine aortic allograft model, SD-208 effectively reduces the formation of intimal hyperplasia of transplant arteriosclerosis (TA)^[3].

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.

352.75

C₁₇H₁₀ClFN₆

627536-09-8

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 9.09 mg/mL (25.77 mM; Need ultrasonic)

*

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: 0.91 mg/mL (2.58 mM); Suspended solution; Need ultrasonic

  此方案可获得 0.91 mg/mL (2.58 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 9.1 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: 0.91 mg/mL (2.58 mM); Suspended solution; Need ultrasonic

  此方案可获得 0.91 mg/mL (2.58 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 9.1 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: ≥ 0.91 mg/mL (2.58 mM); Clear solution

  此方案可获得 ≥ 0.91 mg/mL (2.58 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 9.1 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Uhl M, et al. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004 Nov 1;64(21):7954-61.

  [2]. Ge R, et al. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo. Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4315-30.

  [3]. Sun Y, et al. Inhibition of intimal hyperplasia in murine aortic allografts by the oral administration of the transforming growth factor-beta receptor I kinase inhibitor SD-208. J Heart Lung Transplant. 2014 Jun;33(6):654-61.

Various kinase activities are assayed by measuring the incorporation of radiolabeled ATP into a peptide or protein substrate. The reactions are performed in 96-well plates and included the relevant kinase, substrate, ATP, and appropriate cofactors. The reactions are incubated and then stopped by the addition of phosphoric acid. Substrate is captured onto a phosphocellulose filter, which is washed free of unreacted ATP. The counts incorporated are determined by counting on a microplate scintillation counter. The ability of SD-208 to inhibit the respective kinase is determined by comparing counts incorporated in the presence of compound with those incorporated in the absence of compound.

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.

Glioma cells are cultured in the absence or presence of SD-208 (1 μM) for 48 hours. The cells are pulsed for the last 24 hours with [methyl-³H]thymidine (0.5 μCi) and harvested, and incorporated radioactivity is determined in a liquid scintillation counter.

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.

VM/Dk mice are purchased from the TSE Resource Center. Mice of 6 to 12 weeks of age are used for the survival experiments. Groups of eight mice are anesthesized before all intracranial procedures and placed in a stereotaxic fixation device. A burr hole is drilled in the skull 2 mm lateral to the bregma. The needle of a Hamilton syringe is introduced to a depth of 3 mm. SMA-560 cells [5×10³cells] resuspended in a volume of 2 μL of PBS are injected into the right striatum. Three days later, the mice are allowed to drink SD-208 at 1 mg/mL in deionized water. The mice are observed daily and, in the survival experiments, sacrificed on development of neurologic symptoms.

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.

• [1]. Uhl M, et al. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res. 2004 Nov 1;64(21):7954-61.

  [2]. Ge R, et al. Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-beta type I receptor kinase in vivo. Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4315-30.

  [3]. Sun Y, et al. Inhibition of intimal hyperplasia in murine aortic allografts by the oral administration of the transforming growth factor-beta receptor I kinase inhibitor SD-208. J Heart Lung Transplant. 2014 Jun;33(6):654-61.