Next Article in Journal
Brown Seaweed Egregia menziesii’s Cytotoxic Activity against Brain Cancer Cell Lines
Previous Article in Journal
Metabolic Profiling of Nine Mentha Species and Prediction of Their Antioxidant Properties Using Chemometrics
Article Menu
Issue 2 (January-2) cover image

Export Article

Open AccessArticle
Molecules 2019, 24(2), 259;

Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China
National Glycoengineering Research Center and Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, 27 Shanda Nan Lu, Jinan 250100, China
TaizhouHuayuan Med Tech Company LTD, 1 Yaocheng Avenue, Taizhou 225312, China
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 13 December 2018 / Revised: 5 January 2019 / Accepted: 10 January 2019 / Published: 11 January 2019
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [1976 KB, uploaded 11 January 2019]   |  


‘Biased’ ligands of G protein-coupled receptors (GPCRs) represent a type of promising analgesic with reduced on-target side effects. PZM21, a potent μ-opioid-receptor (μOR)-biased agonist with a new chemical scaffold compared to classic opioids, has been identified as a therapeutic lead molecule for treating pain. In the current study, novel PZM21 analogues were synthesized and evaluated for their in vitro and in vivo efficacy. Novel compound 7a and PZM21 demonstrated undetectable β-arrestin-2 recruitment, however, their analgesic effects need to be further confirmed. Compounds 7b, 7d, and 7g were stronger analgesics than PZM21 in both the mouse formalin injection assay and the writhing test. Compound 7d was the most potent analogue, requiring a dose that was 1/16th to 1/4th of that of PZM21 for its analgesic activity in the two assays, respectively. Therefore, compound 7d could serve as a lead to develop new biased μOR agonists for treating pain. View Full-Text
Keywords: μOR-biased agonist; PZM21; Gi signaling pathway; β-arrestin-2 recruitment; structure–activity relationship μOR-biased agonist; PZM21; Gi signaling pathway; β-arrestin-2 recruitment; structure–activity relationship

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Ma, M.; Sun, J.; Li, M.; Yu, Z.; Cheng, J.; Zhong, B.; Shi, W. Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists. Molecules 2019, 24, 259.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top