Ivarmacitinib (SHR0302) 是一种有效的具有口服活性的JAK抑制剂，尤其是JAK1的抑制剂。Ivarmacitinib 对JAK1的选择性是JAK2的 10 倍以上，是JAK3的 77 倍，是Tyk2的 420 倍。Ivarmacitinib 抑制JAK1-STAT3磷酸化并诱导肝星状细胞凋亡 (apoptosis)。Ivarmacitinib 具有抗增殖和抗炎作用。
| 生物活性 | Ivarmacitinib (SHR0302) is a potent and orally active all members of theJAKfamilyinhibitor, particularlyJAK1. The selectivity of Ivarmacitinib forJAK1is >10-fold forJAK2, 77-fold forJAK3, 420-fold forTyk2. Ivarmacitinib inhibitsJAK1-STAT3phosphorylation and induces theapoptosisof hepatic stellate cells. Ivarmacitinib has anti-proliferative and anti-inflammatory effects[1][2]. |
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体外研究
(In Vitro) | Ivarmacitinib (SHR0302; 1 nM-10 μM; 48 hours; HSCs) treatment displays an inhibitory effect on the proliferation of HSCs in a concentration-dependent manner[2].
Ivarmacitinib (1 nM-10 μM) exerts an inhibitory effect on the activation, proliferation and migration of HSCs[2].
Ivarmacitinib (1 nM-10 μM; 48 hours; HSCs) treatment induces the apoptosis of HSCs[2].
Ivarmacitinib (1 nM-10 μM; 48 hours; HSCs) treatment significantly increases the activation of caspase-3 and Bax in HSCs, and decreases the expression of Bcl-2. SHR0302 also inhibits the activation of Akt signaling pathway[2].
Cell Proliferation Assay[2] | Cell Line: | Hepatic stellate cells (HSCs) | | Concentration: | 1 nM, 10 nM, 100 nM, 1μM, 10 μM | | Incubation Time: | 48 hours | | Result: | Displayed an inhibitory effect on the proliferation of HSCs, and that inhibition ocurred in a concentration-dependent manner. |
Apoptosis Analysis[2] | Cell Line: | Hepatic stellate cells (HSCs) | | Concentration: | 1 nM, 10 nM, 100 nM, 1μM, 10 μM | | Incubation Time: | 48 hours | | Result: | Induced the apoptosis of HSCs. |
Western Blot Analysis[2] | Cell Line: | Hepatic stellate cells (HSCs) | | Concentration: | 1 nM, 10 nM, 100 nM, 1μM, 10 μM | | Incubation Time: | 48 hours | | Result: | Significantly increased the activation of caspase-3 and Bax in HSCs, and decreased the expression of Bcl-2. Also inhibited the activation of Akt signaling pathway. |
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体内研究
(In Vivo) | Ivarmacitinib (SHR0302; 0.3-3.0 mg/kg; intragastric administration; twice a day; for 14 days; male Sprague-Dawley (SD) rats) treatment suppresses the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats[1].
Ivarmacitinib can inhibit the proliferation of T, B and fibroblast-like synoviocytes (FLS), and down-regulates cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppresses the proportion of Th17 and total B, and inhibits JAK1-STAT3 phosphorylation[1].
| Animal Model: | Male Sprague-Dawley (SD) rats (150-180 g) injected with complete Freund’s adjuvant (CFA)[1] | | Dosage: | 0.3 mg/kg,1.0 mg/kg, 3.0 mg/kg | | Administration: | Intragastric administration; twice a day; for 14 days | | Result: | Suppressed the severity of adjuvant-induced arthritis (AA) rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats. |
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| 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 |
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| 溶解性数据 | In Vitro: DMSO : 31.25 mg/mL(75.40 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.4127 mL | 12.0633 mL | 24.1266 mL | | 5 mM | 0.4825 mL | 2.4127 mL | 4.8253 mL | | 10 mM | 0.2413 mL | 1.2063 mL | 2.4127 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: ≥ 2.08 mg/mL (5.02 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.02 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (5.02 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.02 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (5.02 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.02 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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