Tyk2-IN-5 (compound 6) 是一种强效的、具有选择性和口服活性的酪氨酸激酶 2 (Tyk2) 抑制剂，作用于JH2结构域。Tyk2-IN-5 对Tyk2 JH2的Ki值为 0.086 nM，对 IFNα 的IC50值为 25 nM。Tyk2-IN-5 能高效地抑制药效学大鼠模型中 IFNγ 的产生，对大鼠关节炎模型具有完全的疗效。
| 生物活性 | Tyk2-IN-5 (compound 6) is a potent, selective and orally activetyrosine kinase 2(Tyk2) inhibitor that acts on theJH2structural domain. Tyk2-IN-5 shows aKivalue of 0.086 nM forTyk2JH2and anIC50value of 25 nM for IFNα. Tyk2-IN-5 efficiently inhibits the production of IFNγ in a pharmacodynamic rat model and is fully efficacious in a rat model of arthritis[1]. |
| IC50& Target[1] | Tyk2 JH2 0.086 nM (Ki) | IFNα 25 nM (IC50) |
|
体外研究
(In Vitro) | Tyk2-IN-5 inhibits Jak1-3 with IC50values of >2 μM and displays the Jak1-3 dependent cellular activities of >12.5 μM (IC50values)[1].
|
体内研究
(In Vivo) | Tyk2-IN-5 (5, 10 mg/kg; p.o.; twice daily for 20 days) shows highly efficacious in a rat adjuvant arthritis model[1].
Tyk2-IN-5 (1, 10 mg/kg; p.o.; single) inhibits IL-12/IL-18 induced IFNγ production in a dose-dependent manner[1].
Tyk2-IN-5 (10 mg/kg; p.o.; single) shows a high oral exposure and bioavailability (114%) in rat[1].
| Animal Model: | Lewis male rats (rat adjuvant arthritis model)[1]. | | Dosage: | 5, 10 mg/kg | | Administration: | Oral administration; twice daily for 20 days | | Result: | Demonstrated full efficacy to prevent the rats′ paw from swelling. |
| Animal Model: | Lewis male rats (IL-12/IL-18-induced)[1]. | | Dosage: | 1, 10 mg/kg | | Administration: | Oral administration; single | | Result: | Inhibited IL-12/IL-18 induced IFNγ production by 45% and 77% at doses of 1 and 10 mg/kg, respectively. |
| Animal Model: | Lewis male rats, mouse[1]. | | Dosage: | 10 mg/kg | | Administration: | Oral administration; single | | Result: | 1.19Pharmacokinetic Parameters of Tyk2-IN-5 in mouse and rat[1].
| PO (10 mg/kg) | | mouse | rat | | Cmax(μM) | 15 | 9.4 | | AUC0-24(μMoh) | 19 | 57 | | CL (mL/min/kg) | 16 | 7.8 | | F (%) | 86 | 114 |
|
|
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
| 溶解性数据 | In Vitro: DMSO : 43.33 mg/mL(99.74 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.3019 mL | 11.5093 mL | 23.0187 mL | | 5 mM | 0.4604 mL | 2.3019 mL | 4.6037 mL | | 10 mM | 0.2302 mL | 1.1509 mL | 2.3019 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。-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: ≥ 2.17 mg/mL (5.00 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (5.00 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 21.7 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。 *以上所有助溶剂都可在本网站选购。
|
