PZM21

SKU: orb1222546

Description

PZM21 is a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. PZM21 is an experimental opioid analgesic drug that is being researched for the treatment of pain. It is a functionally selective μ-opioid receptor agonist which produces μ-opioid receptor mediated G protein signaling, with potency and efficacy similar to morphine, but with less β-arrestin 2 recruitment. In tests on mice, PZM21 was slightly less potent than morphine or TRV130 as an analgesic, but also had significantly reduced adverse effects, with less constipation than morphine, and very little respiratory depression, even at high doses.

Key Properties

• CAS Number: 1997387-43-5
• MW: 361.5
• Purity: >98% (HPLC)
• Formula: C₁₉H₂₇N₃O₂S
• SMILES: Oc1ccc(cc1)C[C@@H](CNC(=O)N[C@@H](C)Cc2ccsc2)N(C)C
• Target: μ-opioid receptor
• Solubility: DMSO : ≥ 72 mg/mL; 199.17 mM

Bioactivity

• In Vivo:
  PZM21 is a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. PZM21 is efficacious for the affective component of analgesia versus the reflexive component and is devoid of respiratory depression in mice at equi-analgesic doses. PZM21 displays dose-dependent analgesia in a mouse hotplate assay, with a per cent maximal possible effect (% MPE) of 87% reached 15 min after administration of the highest dose of drug tested. PZM21 has a long-lasting analgesic effect on CNS mediated-pain responses, but does not cause respiratory depression and constipation, two key side effects of opioid agonists.
• In Vitro:
  PZM21 has no detectable κOR or nociceptin receptor agonist activity-it is actually an 18 nM κOR antagonist-while it is a 500-fold weaker δOR agonist, making it a selective μOR agonist. At hERG, PZM21 has an IC50 of between 2 and 4 μM, 500- to 1, 000-fold weaker than its potency as a μOR agonist. Signalling by PZM21 and other μOR agonists appears to be mediated primarily by the heterotrimeric G protein Gi/o, as its effect on cAMP levels is eliminated by pertussis toxin and no activity is observed in a calcium release assay.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PZM21 | PZM-21 | PZM 21

Quick Database Links

Gene Symbol

μ-opioid receptor