ELN-441958 是一种有效的、中性的、竞争性的和选择性的缓激肽 B1受体 (bradykinin B1receptor) 拮抗剂，Ki值为 0.26 nM。ELN-441958 具有较高的口服生物利用度，在小鼠中 CNS 透过性低。
| 生物活性 | ELN-441958 is a potent, neutral, competitive and selectivebradykinin B1receptorantagonist with aKiof 0.26 nM against native human bradykinin B1receptor. ELN-441958 has high oral bioavailability, and has low CNS exposure in the mouse[1]. |
| IC50& Target | Ki: 0.26 nM (native human bradykinin B1receptor)[1] |
体外研究
(In Vitro) | ELN-441958 is selective for primate over rodent B1receptors with a rank order potency (KB, nanomolar) of human (0.12 ± 0.02) ~ rhesus monkey (0.24 ± 0.01) >rat (1.5 ± 0.4) >mouse (14 ± 4)[1].
ELN-441958 has good permeability and metabolic stability[1].
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体内研究
(In Vivo) | ELN-441958 (1-10 mg/kg; s.c.; once) dose-dependently reduces carrageenan-induced thermal hyperalgesia in a rhesus monkey tail-withdrawal model[1].
ELN-441958 (0-10 mg/kg; i.v. or p.o.) exhibits a favorable pharmacokinetic profile in the rat and rhesus monkey[1].
| Animal Model: | Adult male and female rhesus monkeys[1] | | Dosage: | 1, 3, or 10 mg/kg | | Administration: | Subcutaneous injection, 30 min before carrageenan injection | | Result: | Increased the tail-withdrawal latencies in a dose-dependent manner. |
| Animal Model: | Rhesus monkeys or Sprague-Dawley rats[1] | | Dosage: | 2.5 or 10 mg/kg for rats, 1 mg/kg or 5 mg/kg for rhesus monkeys | | Administration: | Intravenous injection (2.5 mg/kg and 1 mg/kg) or oral administration (10 mg/kg and 5 mg/kg) (Pharmacokinetic Analysis) | | Result: | In rats: When dosed intravenously, showed a moderate volume of distribution (2.7 L/kg, approximately four times total body water) and a moderate clearance (0.96 L/h/kg, approximately 24% of hepatic blood flow). The terminal plasma half-life of this compound in rats was 1.7 h. When dosed orally, the concentrations increased to a maximum of 1.2 g/mL at 2 h after dosing. The oral availability was 57%.
In rhesus monkeys: When dosed intravenously, showed a moderate volume of distribution (2.7 L/kg) and a moderate clearance (0.49 L/h/kg, approximately 32% of hepatic blood flow). The terminal plasma half-life was 3.9 h. When dosed orally, the concentrations increased to a maximum of 3.6 g/mL at 3.3 h after dosing. The calculated oral bioavailability was greater than 100%. |
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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 : 100 mg/mL(199.59 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9959 mL | 9.9796 mL | 19.9593 mL | | 5 mM | 0.3992 mL | 1.9959 mL | 3.9919 mL | | 10 mM | 0.1996 mL | 0.9980 mL | 1.9959 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: ≥ 2.5 mg/mL (4.99 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.99 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 (4.99 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.99 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 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: ≥ 2.5 mg/mL (4.99 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.99 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 25.0 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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