SC99 是口服有效的，选择性的STAT3抑制剂，靶向 JAK2-STAT3 途径。SC99 结合在 JAK2 的 ATP 结合袋中。SC99 抑制 JAK2 和 STAT3 的磷酸化，而对与 STAT3 信号相关的其他激酶没有影响。SC99 抑制血小板活化、聚集，并显示有效的抗骨髓瘤，抗血栓形成活性。
| 生物活性 | SC99 is an orally active, selectiveSTAT3inhibitor targeting JAK2-STAT3 pathway. SC99 docks into the ATP-binding pocket ofJAK2. SC99 inhibits phosphorylation ofJAK2andSTAT3with no effects on the other kinases associated withSTAT3signaling. SC99 inhibits platelet activation, aggregation and displays potent anti-myeloma, anti-thrombotic activities[1][2][3]. |
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体外研究
(In Vitro) | SC99 (10 or 30 μM; for 72 hours) induces MM cell death[1].
SC99 (10 μM; 24 hours) decreases the p-STAT3 level but has no effects on total STAT3 expression. SC99 (2.5, 5, 10, 20 μM; for 60 mins) inhibits JAK2 phosphorylation in a concentration-dependent manner but does not inhibit the phosphorylation levels of AKT, ERK, mTOR or c-Src at a concentration up to 20 μM[1].
SC99 (1.25, 2.5, 5 μM; pre-treated for 10 min) inhibits collagen (2 μg/mL) and thrombin (0.02 U/mL) induced phosphorylation of STAT3 in a concentration-dependent manner[2].
SC99 (pre-treated for 2 hours) inhibits IL-6 (50 ng/ml; for 20 min) induced STAT3 nuclear translocation in OPM2 cells[3].
Apoptosis Analysis[1] | Cell Line: | Six multiple myeloma (MM) cell lines (LP1, JJN3, RPMI-8226, U266, OPM2 and OCI-MY5) | | Concentration: | 10 or 30 μM | | Incubation Time: | For 72 hours | | Result: | Induced MM cell death. |
Apoptosis Analysis[1] | Cell Line: | MM cell lines[1] | | Concentration: | 10 μM | | Incubation Time: | 24 hours | | Result: | Decreased the p-STAT3 level but had no effects on total STAT3 expression in all cell lines examined. |
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体内研究
(In Vivo) | SC99 (30 mg/kg; orally; daily; for continuous 14 or 28 days) delays myeloma tumor growth in xenograft mice models[1].
SC99 (5, 10, 15 mM, 15 μL; ICV) produces an effective inhibitory effect on the phosphorylation of JAK2 and STAT3 in middle cerebral artery occlusion and reperfusion (MCAO/R) model (adult male SD rats; 250-300 g). SC99 ameliorates neuronal apoptosis and degeneration, neurobehavioral deficits, inflammatory response and brain edema[3].
| Animal Model: | Nude mice with Human MM cells OPM2 or JJN3[1] | | Dosage: | 30 mg/kg | | Administration: | Orally; daily; for continuous 14 or 28 days | | Result: | Delayed myeloma tumor growth in xenograft mice models and suppressed tumor growth more than 40% in 14 days in the OPM2 model. |
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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 : 83.33 mg/mL(247.90 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.9749 mL | 14.8743 mL | 29.7486 mL | | 5 mM | 0.5950 mL | 2.9749 mL | 5.9497 mL | | 10 mM | 0.2975 mL | 1.4874 mL | 2.9749 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 (6.19 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (6.19 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 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 (6.19 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (6.19 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 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。 *以上所有助溶剂都可在本网站选购。
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