SAR-20347 is an inhibitor of TYK2, JAK1, JAK2 and JAK3 with IC₅₀s of 0.6, 23, 26 and 41 nM, respectively.

When NK-92 cells are stimulated with IL-12, SAR-20347 potently inhibits IL-12-mediated STAT4 phosphorylation, a TYK2-dependent event, with an IC₅₀ of 126 nM. SAR-20347 demonstrates a selectivity of TYK2>JAK1>JAK2>JAK3. Cells without IL-12 in the culture media have no measureable IFN-γ, while cells incubated with IL-12 and SAR-20347 demonstrate dose-dependent inhibition of IFN-γ production. SAR-20347 dose-dependently inhibits the production of secreted embryonic alkaline phosphatase (SEAP) with greatest inhibition occurring with 5 μM of SAR-20347 in these experiments^[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.

60 mg/kg SAR-20347 inhibits the production of IFN-γ in the serum by 91% compare to vehicle-treated animals, demonstrating that SAR-20347 can inhibit TYK2 signaling in vivo. SAR-20347 treatment significantly reduces IL-17 production as measured by average signal intensity, consistent with the gene expression analysis^[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.

444.84

C₂₁H₁₈ClFN₄O₄

1450881-55-6

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 : 100 mg/mL (224.80 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 (5.62 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.62 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 (5.62 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.62 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

• [1]. Works MG, et al. Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J Immunol. 2014 Oct 1;193(7):3278-87.

Kinases are prepared in Base Reaction Buffer (20 mM Hepes pH 7.5, 10 mM MgCl₂, 1 mM EGTA, 0.02% Brij35, 0.02 mg/mL BSA, 0.1 mM Na₃VO₄, 2 mM DTT, 1% DMSO) and substrate is added with 1.5 mM CaCl₂, 16 μg/mL Calmodulin, and 2 mM MnCl₂. Varying concentrations of SAR-20347 in DMSO are added to the kinase reaction along with 10 μM ³³P-ATP (activity 0.01 μCi/μL final) for IC₅₀ determination^[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.

Cells are plated in a 96-well v-bottom plate in starvation medium, incubated with SAR-20347 (0.5% DMSO) for 20 minutes at 37°C, 5% CO₂, and stimulated with individual cytokines. P-STAT levels are measured in duplicate using MSD plates following the manufacturer’s instructions (MSD). The IC₅₀ is determined by subtracting background (no cytokine) and relative to DMSO/cytokine control^[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.

Female 7 to 9 week old C57BL/6 mice are used. Mice are administered vehicle or 50 mg/kg SAR-20347 by oral gavage 30 minutes prior to application of 62.5 mg 5% imiquimod cream or control cream. Another dose of vehicle or 50 mg/kg SAR-20347 is given 5.5 hours following the first dose. This treatment is repeated for 5 days and on day 3 and 4, animals are injected with 100 uL saline to prevent dehydration. Each day, the mice are assessed by the same researcher for redness. On the 6^th day, the animals are euthanized and photographs are taken^[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.

• [1]. Works MG, et al. Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J Immunol. 2014 Oct 1;193(7):3278-87.