(-)-U-50488 hydrochloride (Synonyms: (-)-Trans-(1S,2S)-U-50488 hydrochloride) |
| Katalog-Nr.GC15944 |
(-)-U-50488 hydrochloride is a selective agonist of the kappa opioid receptor (KOR) with an IC50 value of 0.25μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 114528-79-9
Sample solution is provided at 25 µL, 10mM.
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(-)-U-50488 hydrochloride is a selective agonist of the kappa opioid receptor (KOR) with an IC50 value of 0.25μM[1]. (-)-U-50488 hydrochloride activates KOR, which has been implicated in physiological processes studied in pain modulation, emotion regulation, and addiction[1]. (-)-U-50488 hydrochloride has been mainly used to study behavioral effects, stress response, and cognitive function in animal models[2].
In vitro, human monocyte-derived macrophages (MDM) cultures were established for HIV-1 infection[3]. (-)-U-50488 hydrochloride (30pg/ml) was added to MDM culture media, and supernatant was harvested on day 7 and day 14 post infection to evaluate the direct effect of KOR activation on HIV-1 expression[3]. Addition of (-)-U-50488 hydrochloride (0.1pM) significantly inhibited HIV-1 expression both at day 7 and day 14 after infection[3]. Pretreatment of 1pM Nor-BNI inhibiting KOR activation decreased the inhibitory effect of (-)-U-50488 hydrochloride (0.1pM) on HIV-1 expression by >65%[3]. Therefore, anti-HIV-1 effect of (-)-U-50488 hydrochloride was regulated by KOR activation[3].
In vivo, adult C57BL/6J mice (6 female and 6 male) were euthanized, and 300μm thick coronal brain sections were prepared to investigate the effects of (-)-U-50488 hydrochloride on dopamine release[4]. 10, 30, 100, 300, 1000nM of (-)-U-50488 hydrochloride were bath applied to sections, and KOR agonist curve responding to dopamine were analyzed[4,5]. Activation of KOR inhibited dopamine release, with no observed sex differences in mice[4]. Moreover, treatment with (-)-U-50488 hydrochloride did not affect dopamine uptake in any of the nucleus accumbens core subregions[4].
References:
[1]Zhao Y, Joshi AA, Aldrich JV, Murray TF. Quantification of kappa opioid receptor ligand potency, efficacy and desensitization using a real-time membrane potential assay. Biomedicine & Pharmacotherapy. 2021 Nov 1;143:112173.
[2]Callaghan CK, Rouine J, Islam MN, Eyerman DJ, Smith KL, Blumberg L, Sanchez C, O’Mara SM. Differential effects of opioid receptor modulators on motivational and stress-coping behaviors in the back-translational rat IFN-α depression model. bioRxiv. 2019 Sep 28:769349.
[3]Chao CC, Gekker G, Sheng WS, Hu S, Peterson PK. U50488 inhibits HIV-1 expression in acutely infected monocyte-derived macrophages. Drug and alcohol dependence. 2001 Apr 1;62(2):149-54.
[4]Karkhanis AN, West AM, Jones SR. Kappa opioid receptor agonist U50, 488 inhibits dopamine more in caudal than rostral nucleus accumbens core. Basic & clinical pharmacology & toxicology. 2023 Nov;133(5):526-34.
[5]Karkhanis AN, Rose JH, Weiner JL, Jones SR. Early-life social isolation stress increases kappa opioid receptor responsiveness and downregulates the dopamine system. Neuropsychopharmacology. 2016 Aug;41(9):2263-74.
| Cell experiment [1]: | |
Cell lines | Human monocyte-derived macrophage (MDM) cells |
Preparation Method | Human monocyte-derived macrophage (MDM) cells were isolated from blood monocytes[1]. MDM cells were incubated in RPMI-1640 media[1]. Some MDM cells were pretreated with 1pM Nor-BNI[1]. MDM cells were then treated with 30pg/ml (-)-U-50488 hydrochloride for 24h, followed by infection with HIV-1SF162 at an infection of 0.02 for an additional 24h[1]. After washing off the media, 30pg/ml (-)-U-50488 hydrochloride was added back to cells media, and supernatants were harvested on day 7 or 14 post-infection for HIV-1 p24 antigen (Ag) levels assay check[1]. |
Reaction Conditions | (-)-U-50488 hydrochloride: 30pg/ml; 24h, Day 7, Day 14; Nor-BNI: 1pM |
Applications | Addition of (-)-U-50488 hydrochloride (0.1pM) significantly inhibited HIV-1 expression both at day 7 and day 14 after infection. Pretreatment of 1pM Nor-BNI inhibiting KOR activation decreased the inhibitory effect of (-)-U-50488 hydrochloride (0.1pM) on HIV-1 expression by >65%. |
| Animal experiment [2,3]: | |
Animal models | C57BL/6J male and female mice |
Preparation Method | Preparation Method Mice were euthanized, and brains were removed. The vibrating tissue slicer was used to prepare 300μm thick coronal brain sections[2]. Endogenous dopamine release was evoked by single electrical pulse (350μA) stimulation every 5min at the rate of 400V/s[2]. After stable dopamine was obtained, 10, 30, 100, 300, 1000nM of (-)-U-50488 hydrochloride were bath applied to coronal brain sections[2,3]. KOR agonist curve responding to dopamine were analyzed[2]. |
Dosage form | (-)-U-50488 hydrochloride: 10, 30, 100, 300, 1000nM |
Applications | Activation of KOR inhibited dopamine release, with no observed sex differences in mice. Treatment with (-)-U-50488 hydrochloride did not affect dopamine uptake in any of the nucleus accumbens core subregions. |
References: | |
| Cas No. | 114528-79-9 | SDF | |
| Überlieferungen | (-)-Trans-(1S,2S)-U-50488 hydrochloride | ||
| Chemical Name | 2-(3,4-dichlorophenyl)-N-methyl-N-((1R,2R)-2-(pyrrolidin-1-yl)cyclohexyl)acetamide hydrochloride | ||
| Canonical SMILES | CN(C(CC1=CC(Cl)=C(Cl)C=C1)=O)[C@]2([H])CCCC[C@@]2([H])N3CCCC3.Cl | ||
| Formula | C19H26Cl2N2O.HCl.¼H2O | M.Wt | 410.29 |
| Löslichkeit | Water to 100 mM; DMSO to 100 mM | Storage | Desiccate at RT |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4373 mL | 12.1865 mL | 24.373 mL |
| 5 mM | 0.4875 mL | 2.4373 mL | 4.8746 mL |
| 10 mM | 0.2437 mL | 1.2187 mL | 2.4373 mL |
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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