Navacaprant (BTRX-335140) 是一种选择性的,具有口服活性的κ opioid receptor (KOR)拮抗剂,对 κOR,μOR 和 δOR 具有拮抗活性,IC50值分别为 0.8 nM,110 nM 和 6500 nM。Navacaprant 在大鼠中具有良好的体外 ADMET 和体内药代动力学特征。Navacaprant 可以很好地分布到 CNS 中,可用于神经病变类的研究。
生物活性 | Navacaprant (BTRX-335140) is a selective and orally activeκopioid receptor(KOR)antagonist, has antagonist activity for κOR, μOR and δOR withIC50values of 0.8 nM, 110 nM, and 6500 nM, respectively.
Navacaprant endows with favorable in vitro ADMET and in vivo pharmacokinetic profiles and medication-like duration of action in rats. Navacaprant distributes well into the CNS and can be used for the research of neuropathy[1]. |
IC50& Target | κ Opioid Receptor/KOR 0.8 nM (IC50) | μ Opioid Receptor/MOR 110 nM (IC50) | δ Opioid Receptor/DOR 6500 nM (IC50) |
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体外研究 (In Vitro) | Navacaprant (BTRX-335140) (0-10 μM; 4 h) shows selective antagonist activity towards Kappa Opioid Receptor[1].
Cell Viability Assay[1] Cell Line: | OPRK1-BLA U2OS cells | Concentration: | 0-10 μM | Incubation Time: | 4 hours | Result: | Exibited antagonist activity to KOR, DOR and MOR with IC50values of 0.8, 110 and 6500 nM respectively, and showed selective antagonist activity to KOR. |
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体内研究 (In Vivo) | Navacaprant (BTRX-335140) (0.01-3 mg/kg; p.o. once) reduces U69,593- stimulated plasma prolactin secretion to levels of without U69,593 treatment[1].Navacaprant (BTRX-335140) (1 mg/kg; i.p. once) blocks U-50488-induced antinociception from hot water[1]. 1.19Pharmacokinetic Parameters of BTRX-335140 in rodents[1]. | Rats IV 1 mg/kg | Mice IV 3 mg/kg | Rats PO 5 mg/kg | Mice PO 10 mg/kg | CL (mL/min/kg) | 105 | 66.5 | | | t1/2(h) | 1.81 | 1.91 | 6.19 | 2.57 | AUC0-t(hong/mL) | 153 | 725 | 265 | 232 | Vss(L/kg) | 13.8 | 7.72 | | | F (%) | | | 30.2 | 12 |
Animal Model: | Rat PRL model[1] | Dosage: | 0.01, 0.03, 0.1, 0.3, 1 and 3 mg/kg | Administration: | Oral gavage; 0.01-3 mg/kg once | Result: | Effectively decreased the high level prolactin caused by U69,593 even at a dosage of 0.1 mg/kg. |
Animal Model: | Adult male ICR mice with tail dipped into 50℃ hot water[1] | Dosage: | 1 mg/kg | Administration: | Intraperitoneal injection; 1 mg/kg once | Result: | Blocked the U-50488-induced antinociception at 1 h but not at 24 h pretreatment time and showed a medication-like duration of action in blocking the KOR. |
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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 : 16.67 mg/mL(36.75 mM;Need ultrasonic) 配制储备液 1 mM | 2.2048 mL | 11.0241 mL | 22.0483 mL | 5 mM | 0.4410 mL | 2.2048 mL | 4.4097 mL | 10 mM | 0.2205 mL | 1.1024 mL | 2.2048 mL |
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此方案可获得 ≥ 1.67 mg/mL (3.68 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 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 1 mg/mL (2.20 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (2.20 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 10.0 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。 3. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 1 mg/mL (2.20 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (2.20 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 10.0 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。 *以上所有助溶剂都可在本网站选购。
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