Naltrindole hydrochloride is a highly potent and selective non-peptide δ opioid receptor antagonist with a K_i of 0.02 nM.

Ki: 0.02 nM (δ opioid), 64 nM (μ opioid), 66 nM (κ opioid)^[1]

Opioid drugs exert a wide spectrum of physiological and behavioral effects. These effects are mediated via membrane-bound receptors, of which the best characterized are the kappa, delta, and mu receptors^[1]. Naltrindole inhibits the proliferation of cultured human U266 MM cells in a time- and dose-dependent manner with an EC₅₀ of 16 μM. Treatment of U266 cells with naltrindole significantly decreases the level of the active, phosphorylated form of the kinases, extracellular signal-regulated kinase and Akt, which may be related to its antiproliferative activity^[2]. Naltrindole inhibits growth and induces apoptosis in the three characteristic SCLC cell lines, NCI-H69, NCI-H345, and NCI-H510. Naltrindole treatment reduces constitutive phosphorylation of Akt/PKB on serine 473 and threonine 308 in cells and also its downstream effectors glycogen synthase kinase-3β and the Forkhead transcription factors AFX and FKHR^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Naltrindole significantly decreases tumor cell volumes in human MM cell xenografts in severe combined immunodeficient mice^[2]. In mice, naltrindole at 20 mg/kg s.c. antagonizes the δ-selective agonist effect of [D- Ser, Leu, Thr]enkephalin (DSLET) without blocking the antinociceptive effect of morphine or U50488H. Naltrindole is the only highly selective δ antagonist that is active upon peripheral administration^[4]. Acute naltrindole induces significant decreases in external and total ambulation (horizontal activity) and rearing behaviour (vertical activity), as well as a significant increase in grooming frequency. In animals chronically treated with naltrindole there is an increase in total ambulation one day after the discontinuation of the treatment^[5].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

450.96

C₂₆H₂₇ClN₂O₃

111469-81-9

纳曲吲哚盐酸盐

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : ≥ 188 mg/mL (416.89 mM)

H₂O : 16.67 mg/mL (36.97 mM; ultrasonic and warming and heat to 60°C)

* “≥” means soluble, but saturation unknown.

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°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

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 (5.54 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.54 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。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.54 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.54 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 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.54 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.54 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。

• [1]. Raynor K, et al. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4.

  [2]. Mundra JJ, et al. Naltrindole inhibits human multiple myeloma cell proliferation in vitro and in a murine xenograft model in vivo. J Pharmacol Exp Ther. 2012 Aug;342(2):273-87.

  [3]. Chen YL, et al. Inhibition of akt/protein kinase B signaling by naltrindole in small cell lung cancer cells.

  [4]. Portoghese PS, et al. Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist. Eur J Pharmacol. 1988 Jan 27;146(1):185-6.

  [5]. Fernández B, et al. Postnatal naltrindole treatments induce behavioural modifications in preweanling rats. Neurosci Lett. 2000 Mar 31;283(1):73-6.

U266 cells are plated in 96-well plates at 2000 cells per well in 100 μL of RPMI 1640 medium, supplemented with 10% fetal bovine serum, 100 U/mL penicillin, and 100 μg/mL streptomycin sulfate. Cells are incubated in quadruplicate in the presence of the various antineoplastic agents to construct dose-response curves, alone or in combination with various doses of naltrindole. At the end of the incubation 10 μL of WST-1 cell proliferation reagent is added to each well, and the plates are returned to the incubator for 1 h. Absorbance is then measured^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Rats:
Effects of neonatal naltrindole treatments on open field activity is tested in 20-day old rats. The animals are injected chronically with saline or naltrindole (1 mg/kg, s.c.) (from birth to day 19), and 1 day after the discontinuation of this treatment are studied for the acute effects of naltrindole (1 mg/kg, i.p.)^[5].

Mice:
Naltrindole is dissolved in distilled water to make a 3 mg/mL solution, and mice are injected with 10 mL/kg daily. Human RPMI 8226 multiple myeloma cells are inoculated subcutaneously into both flanks of SCID mice (10 million cells per flank). After 8 days, 12 mice are divided into two groups of six mice each: vehicle-injected and naltrindole-injected (30 mg/kg). Animals are dosed daily for 36 days, and body weights and xenograft tumors are measured twice a week with a digital caliper^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Raynor K, et al. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol. 1994 Feb;45(2):330-4.

  [2]. Mundra JJ, et al. Naltrindole inhibits human multiple myeloma cell proliferation in vitro and in a murine xenograft model in vivo. J Pharmacol Exp Ther. 2012 Aug;342(2):273-87.

  [3]. Chen YL, et al. Inhibition of akt/protein kinase B signaling by naltrindole in small cell lung cancer cells.

  [4]. Portoghese PS, et al. Naltrindole, a highly selective and potent non-peptide delta opioid receptor antagonist. Eur J Pharmacol. 1988 Jan 27;146(1):185-6.

  [5]. Fernández B, et al. Postnatal naltrindole treatments induce behavioural modifications in preweanling rats. Neurosci Lett. 2000 Mar 31;283(1):73-6.