R406 是一种有效的，具有口服活性的，ATP竞争性的Syk/FLT3抑制剂，Ki为 30 nM，有效抑制 Syk 激酶活性，IC50为 41 nM。R406 可减轻免疫复合物介导的炎症。R406 还抑制 Lyn (IC50=63 nM) 和 Lck (IC50=37 nM).
| 生物活性 | R406 is an orally available and competitiveSyk/FLT3inhibitor for ATP binding with aKiof 30 nM, potently inhibitsSykkinase activity in vitro with anIC50of 41 nM, measured at an ATP concentration corresponding to its Kmvalue. R406 reduces immune complex-mediated inflammation[1]. R406 also inhibits Lyn (IC50=63 nM) and Lck (IC50=37 nM)[2]. |
| IC50& Target | Ki: 30 nM (Syk)[1]
IC50: 41 nM (Syk)[1]
FLT3[1]
IC50: 63 nM (Lyn), 37 nM (Lck)[2] |
体外研究
(In Vitro) | R406 inhibits adenosine A3 receptor (IC50=0.081 μM), adenosine transporter (IC50=1.84 μM), and monoamine transporter (IC50=2.74 μM)[1].
R406 inhibits Huh7 hepatocyte, A549 epithelial, and H1299 lung cancer lines with EC50s of 15.1, 2.9 and 6.3 μM, respectively[1].
R406 inhibits phosphorylation of Syk substrate LAT in mast cells and BLNK/SLP65 in B cells[1].
Western Blot Analysis[1] | Cell Line: | Cultured human mast cells (CHMC) | | Concentration: | 0.016, 0.08, 0.4, 2 μM | | Incubation Time: | 40 minutes | | Result: | Inhibited all other kinases tested at 5 to 100 fold less potency than Syk as judged by phosphorylation of target proteins. |
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体内研究
(In Vivo) | R406 (5 and 10 mg/kg) shows efficacy in the amelioration of the Arthus reaction and in reducing clinical symptoms in the collagen antibody-induced arthritis (CAIA) and K/BxN models of rheumatoid arthritis (RA). Immune complex (IC)-mediated inflammation is reduced by inhibition of Fc receptor signaling with R406[1].
| Animal Model: | Female Balb/c mice (6-8 weeks) with CAIA[1] | | Dosage: | 5 and 10 mg/kg | | Administration: | Administered orally, b.i.d, for 14 days, starting 4 hours after antibody challenge on day 0. | | Result: | Reduced inflammation and swelling, and the arthritis progressed more slowly in treated animals than in vehicle controls. |
| Animal Model: | Female C57BL/6 mice with arthritis[1] | | Dosage: | 10 mg/kg | | Administration: | Administered orally one hour before serum injection; b.i.d; for 13 days | | Result: | Delayed the onset and reduced the severity of clinical arthritis. Paw thickening and clinical arthritis were reduced by approximately 50%. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : ≥ 61 mg/mL(97.04 mM) H2O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.5908 mL | 7.9538 mL | 15.9076 mL | | 5 mM | 0.3182 mL | 1.5908 mL | 3.1815 mL | | 10 mM | 0.1591 mL | 0.7954 mL | 1.5908 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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 (3.98 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (3.98 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (3.98 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (3.98 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。 *以上所有助溶剂都可在本网站选购。
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