GS-444217 is a potent, orally available and selective ATP-competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with an IC₅₀ of 2.87 nM^[1].

Treatment with GS-444217 reduces ASK1 phosphorylation and prevents the phosphorylation of MKK3/6, MKK4, p38, and JNK at concentrations of 0.3 μM and above with full suppression of ASK1 activity at 1 μM. GS-444217 (1 μM) reduces ASK1 activity within 5 minutes of addition to the cultures, reaching a maximum level of inhibition by 30 minutes. Removal of GS-444217 from the cultures results in reactivation of ASK1 autophosphorylation within 10 minutes and near-complete recovery 2 hours after drug washout^[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.

GS-444217 reduces oxidative stress (OS)-induced ASK1 signaling in kidney and inhibits acute renal tubular injury in rats. GS-444217 (30 mg/kg) inhibits activation of ASK1, p38, and JNK in rat kidney. GS-444217 has an in vivo EC₅₀ of approximately 1.6 μM for inhibiting the ASK1 pathway in rodent kidney^[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.

411.46

C₂₃H₂₁N₇O

1262041-49-5

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 : 15.5 mg/mL (37.67 mM; Need ultrasonic and warming)

*

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 (6.08 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.08 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 (6.08 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.08 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 (6.08 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.08 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。

• [1]. Liles JT, et al. ASK1 contributes to fibrosis and dysfunction in models of kidney disease. J Clin Invest. 2018 Oct 1;128(10):4485-4500.

  [2]. Budas GR, et al. ASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2018 Feb 1;197(3):373-385.