BAY-985 是一种高效的,有口服活性的、ATP 竞争性的,选择性TBK1和IKKε双重抑制剂,对 TBK1 (在低/高 ATP 实验中) 和 IKKε 的IC50分别为 2/30 和 2 nM。BAY-985 具有抗肿瘤功效。
生物活性 | BAY-985 is a highly potent, orally active and selective ATP-competitive dual inhibitor ofTBK1andIKKεwithIC50s of 2/30 and 2 nM forTBK1(low/high ATP) andIKKε, respectively. Antitumor efficacy[1]. |
IC50& Target[1] | TBK1 2 nM (IC50, low ATP) | TBK1 30 nM (IC50, high ATP) | IKKε 2 nM (IC50) |
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体外研究 (In Vitro) | BAY-985 inhibits FLT3, RSK4, DRAK1, and ULK1 with IC50s of 123, 276, 311, and 7930 nM, respectively[1]. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 (IRF3) with an IC50of 74 nM[1]. BAY-985 is active in cellular mechanistic assay and shows anti-proliferative activity in a few cancer cell lines with IC50s of 900 and 7260 nM for SK-MEL2 (NRAS and TP53 mutated) and ACHN (CDKN2A mutated) cells, respectively[1].
Cell Proliferation Assay[1] Cell Line: | ACHN and SK-MEL-2 cell lines | Concentration: | | Incubation Time: | 96 hours | Result: | Inhibited proliferation in SK-MEL2 and ACHN cells with IC50s of 900 and 7260 nM, respectively. |
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体内研究 (In Vivo) | BAY-985 (200 mg/kg; p.o.; b.i.d.; 111 days) results in weak antitumor efficacy[1]. BAY-985 shows high clearance (CLb= 4.0 L/h/kg, ca. 95% hepatic extraction), large volume of distribution at steady state (Vss=2.9 L/kg) and a short terminal half-life (t1/2=0.79 h)[1].
Animal Model: | Female NMRI nude mice bearing SK-MEL-2 human melanoma xenograft model[1] | Dosage: | 200 mg/kg | Administration: | Applied p.o.; twice daily (b.i.d.) continuously 111 days | Result: | Treatment resulted in weak antitumor efficacy with a T/Ctumor weightratio of 0.6. The treatment was well tolerated, with a maximum body weight loss of less than 10%. |
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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 : 50 mg/mL(90.32 mM;Need ultrasonic) 配制储备液 1 mM | 1.8064 mL | 9.0321 mL | 18.0642 mL | 5 mM | 0.3613 mL | 1.8064 mL | 3.6128 mL | 10 mM | 0.1806 mL | 0.9032 mL | 1.8064 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 (3.76 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.76 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 (3.76 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.76 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 (3.76 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.76 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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