Selective opioid growth factor receptor antagonists based on a stilbene isostere

被引：7
作者：
Stockdale, David P. [1 ]
Titunick, Michelle B. [2 ]
Biegler, Jessica M. [3 ,4 ]
Reed, Jessie L. [3 ,4 ]
Hartung, Alyssa M. [1 ]
Wiemer, David F. [1 ]
McLaughlin, Patricia J. [2 ,4 ]
Neighbors, Jeffrey D. [3 ,4 ]
机构：
[1] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA
[2] Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA
[3] Penn State Univ, Coll Med, Dept Med & Pharmacol, Hershey, PA 17033 USA
[4] Penn State Univ, Inst Canc, Hershey, PA 17033 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 16期
关键词：
Opioid receptor; Opioid growth factor; Low-dose naltrexone; Pawhuskin; Stilbene isostere; LOW-DOSE NALTREXONE; HUMAN OVARIAN-CANCER; CELL-PROLIFERATION; PANCREATIC-CANCER; FACTOR OGF; MECHANISTIC INSIGHTS; AXIS; PHARMACOLOGY; STRESS; MODULATION;
D O I：
10.1016/j.bmc.2017.06.035
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
As part of an ongoing drug development effort aimed at selective opioid receptor ligands based on the pawhuskin natural products we have synthesized a small set of amide isosteres. These amides were centered on lead compounds which are selective antagonists for the delta and kappa opioid receptors. The amide isomers revealed here show dramatically different activity from the parent stilbene compounds. Three of the isomers synthesized showed antagonist activity for the opioid growth factor (OGF)/opioid growth factor receptor (OGFR) axis which is involved in cellular and organ growth control. This cellular signaling mechanism is targeted by "low-dose" naltrexone therapy which is being tested clinically for multiple sclerosis, Crohn's disease, cancer, and wound healing disorders. The compounds described here are the first selective small molecule ligands for the OGF/OGFR system and will serve as important leads and probes for further study. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4464 / 4474
页数：11
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