PZM21 - Opioid Receptor Agonist - 生命科學試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPZM21Cat. No.: HY-101386CAS No.: 1997387-43-5分式: CHNOS分量: 361.5作靶點: Opioid Receptor作通路: GPCR/G Protein; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 72 mg/mL (199.17 mM

2、)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.7663 mL 13.8313 mL 27.6625 mL5 mM 0.5533 mL 2.7663 mL 5.5325 mL10 mM 0.2766 mL 1.3831 mL 2.7663 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內實驗 PZM21 is dissolved in 100% DMSO and further diluted in sali

3、ne containing 1% DMSO3.BIOLOGICAL ACTIVITY物活性 PZM21效選擇性的 opioid receptor受體激動劑，EC50值為1.8 nM。IC50 & Target EC50: 1.8 nM ( opioid receptor) 11/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 PZM21 has no detectable OR or nociceptin receptor agonist activity-it is actually an 18 nM OR antagonist-whi

4、le it is a 500-fold weaker OR agonist, making it a selective OR agonist. At hERG, PZM21 has an IC50of between 2 and 4 M, 500- to 1,000-fold weaker than its potency as a OR agonist. Signalling by PZM21and other OR agonists appears to be mediated primarily by the heterotrimeric G protein Gi/o, as its

5、effect oncAMP levels is eliminated by pertussis toxin and no activity is observed in a calcium release assay 1.體內研究 PZM21 is a potent Gi activator with exceptional selectivity for OR and minimal -arrestin-2 recruitment.Unlike morphine, PZM21 is more efficacious for the affective component of analges

6、ia versus the reflexivecomponent and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 displays dose-dependent analgesia in a mouse hotplate assay, with a per centmaximal possible effect (% MPE) of 87% reached 15 min after administ

7、ration of the highest dose of drugtested 1.PZM21 has a long-lasting analgesic effect on CNS mediated-pain responses, but does not causerespiratory depression and constipation, two key side effects of opioid agonists. PZM21 does not exhibit thetype of biomarker responses, such as hyperlocomotion or c

8、onditioned place preference response, that areobserved when morphine and other opioids are used and are associated with reinforcement and addiction2.PROTOCOLAnimal Mice: PZM21 is dissolved in 0.9% sodium chloride. Mice are injected with either vehicle, morphine (5 mg/kg,Administration 1 or 10 mg/kg)

9、, TRV130 (1.2 mg/kg) or PZM21 (10 mg/kg; 20 mg/kg; or 40 mg/kg). After injection of drug, theanalgesic effect expressed as percentage maximum possible effect (%MPE) is measured at 15, 30, 60, 90and 120 min after drug treatment 1.MCE has not independently confirmed the accuracy of these methods. They

10、 are for reference only.戶使本產品發(fā)表的科研獻 Br J Pharmacol. 2019 May 9. Neuroscience. 2018 Oct 17;394:60-71. bioRxiv. Oct 17, 2018.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Manglik A, et al. Structure-based discovery of opioid analgesics with reduced side effects. Nature. 2016 Se

11、p 8;537(7619):185-190.2. Kostic M, et al. Biasing Opioid Receptors and Cholesterol as a Player in Developmental Biology.3. Araldi D, et al. Mu-opioid Receptor (MOR) Biased Agonists Induce Biphasic Dose-dependent Hyperalgesia and Analgesia, andHyperalgesic Priming in the Rat. Neuroscience. 2018 Oct 17;394:60-71.McePdfHeightCaution: Product has not