JAK3-IN-1 is a potent, selective and orally activeJAK3inhibitor with anIC₅₀of 4.8 nM. JAK3-IN-1 shows over 180-fold more selective forJAK3thanJAK1(IC₅₀of 896 nM) andJAK2(IC₅₀of 1050 nM)^[1].

JAK3-IN-1(Compound 9; 0-5 μM; 3 hours; BMDMs cells) treatment completely inhibits IL-4 induced p-STAT6 at a concentration of 500 nM and only partially inhibits IFNβ-induced p-STAT1 at a concentration of 5.0 μM^[1].
. JAK3-IN-1(Compound 9) most potently inhibits JAK3 and identified fms-related tyrosine kinase 3 (FLT3) and several tyrosine protein kinase (TEC)-family kinases as being potential off-targets. Enzymatic assays using the Z’-lyte or LanthaScreen formats confirmed enzymatic inhibition of FLT3 (IC₅₀= 13 nM), TTK protein kinase (TTK, IC₅₀= 49 nM), BLK proto-oncogene (BLK, IC₅₀= 157 nM) and tyrosine protein kinase TXK (TXK, IC₅₀= 36 nM). JAK3-IN-1 shows very low inhibition scores for other JAKs and wild-type (WT) EGFR, which is consistent with the over 180-fold higher IC₅₀s against EGFRWT and TYK2 (IC₅₀s =409 nM, >10000 respectively). JAK3-IN-1 possesses over 165-fold higher IC₅₀s for BTK or ITK (IC₅₀s = 794 and 1070 nM respectively)^[1].
JAK3-IN-1(Compound 9) selectively inhibits the proliferation of JAK3-dependent Ba/F3 cells (IC₅₀= 69 nM) relative to other JAK-dependent Ba/F3 cells, for which there was no antiproliferative effect at concentrations below 3.0 μM^[1].

JAK3-IN-1(Compound 9) shows reasonable pharmacokinetic properties, with moderate T_1/2of 1.4 h, area under the curve (AUC) value of 795 ng*hr/mL following a 10 mg/Kg oral dose and good oral bioavailability of 66%. After oral administration with JAK3-IN-1(Compound 9) (75 mpk, QD) for 8 days, the numbers of B or T lymphocytes in the tumor-bearing lungs and spleens of treated mice is not affected, however, the number of NK cells is reduced^[1].

508.02

Solid

C₂₆H₃₀ClN₇O₂

1805787-93-2

Room temperature in continental US; may vary elsewhere.

DMSO : 100 mg/mL(196.84 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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

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 (4.92 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.92 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-CDin saline)

  Solubility: 2.5 mg/mL (4.92 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (4.92 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 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 (4.92 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.92 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。