DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1

DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1

Abstract Microsomal prostaglandin E2 synthase-1 (mPGES-1) is known as an ideal target for next generation of anti-inflammatory drugs without the side effects of currently available anti-inflammatory drugs. However, there has been no clinically promising mPGES-1 inhibitor identified through tradition...

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Main Authors: Shuo Zhou, Ziyuan Zhou, Kai Ding, Yaxia Yuan, Charles Loftin, Fang Zheng, Chang-Guo Zhan
Format: Article
Language:English
Published: Nature Publishing Group 2020-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-67283-0
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spelling doaj-6b1699a55ab84411a029ef331c7ca2c52021-06-27T11:36:46ZengNature Publishing GroupScientific Reports2045-23222020-06-011011910.1038/s41598-020-67283-0DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1Shuo Zhou0Ziyuan Zhou1Kai Ding2Yaxia Yuan3Charles Loftin4Fang Zheng5Chang-Guo Zhan6Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone StreetMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone StreetMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone StreetMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone StreetDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone StreetMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone StreetMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone StreetAbstract Microsomal prostaglandin E2 synthase-1 (mPGES-1) is known as an ideal target for next generation of anti-inflammatory drugs without the side effects of currently available anti-inflammatory drugs. However, there has been no clinically promising mPGES-1 inhibitor identified through traditional drug discovery and development route. Here we report a new approach, called DREAM-in-CDM (Drug Repurposing Effort Applying Integrated Modeling-in vitro/vivo-Clinical Data Mining), to identify an FDA-approved drug suitable for use as an effective analgesic targeting mPGES-1. The DREAM-in-CDM approach consists of three steps: computational screening of FDA-approved drugs; in vitro and/or in vivo assays; and clinical data mining. By using the DREAM-in-CDM approach, lapatinib has been identified as a promising mPGES-1 inhibitor which may have significant anti-inflammatory effects to relieve various forms of pain and possibly treat various inflammation conditions involved in other inflammation-related diseases such as the lung inflammation caused by the newly identified COVID-19. We anticipate that the DREAM-in-CDM approach will be used to repurpose FDA-approved drugs for various new therapeutic indications associated with new targets.https://doi.org/10.1038/s41598-020-67283-0
collection DOAJ
language English
format Article
sources DOAJ
author Shuo Zhou
Ziyuan Zhou
Kai Ding
Yaxia Yuan
Charles Loftin
Fang Zheng
Chang-Guo Zhan
spellingShingle Shuo Zhou
Ziyuan Zhou
Kai Ding
Yaxia Yuan
Charles Loftin
Fang Zheng
Chang-Guo Zhan
DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1
Scientific Reports
author_facet Shuo Zhou
Ziyuan Zhou
Kai Ding
Yaxia Yuan
Charles Loftin
Fang Zheng
Chang-Guo Zhan
author_sort Shuo Zhou
title DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1
title_short DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1
title_full DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1
title_fullStr DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1
title_full_unstemmed DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1
title_sort dream-in-cdm approach and identification of a new generation of anti-inflammatory drugs targeting mpges-1
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2020-06-01
description Abstract Microsomal prostaglandin E2 synthase-1 (mPGES-1) is known as an ideal target for next generation of anti-inflammatory drugs without the side effects of currently available anti-inflammatory drugs. However, there has been no clinically promising mPGES-1 inhibitor identified through traditional drug discovery and development route. Here we report a new approach, called DREAM-in-CDM (Drug Repurposing Effort Applying Integrated Modeling-in vitro/vivo-Clinical Data Mining), to identify an FDA-approved drug suitable for use as an effective analgesic targeting mPGES-1. The DREAM-in-CDM approach consists of three steps: computational screening of FDA-approved drugs; in vitro and/or in vivo assays; and clinical data mining. By using the DREAM-in-CDM approach, lapatinib has been identified as a promising mPGES-1 inhibitor which may have significant anti-inflammatory effects to relieve various forms of pain and possibly treat various inflammation conditions involved in other inflammation-related diseases such as the lung inflammation caused by the newly identified COVID-19. We anticipate that the DREAM-in-CDM approach will be used to repurpose FDA-approved drugs for various new therapeutic indications associated with new targets.
url https://doi.org/10.1038/s41598-020-67283-0
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