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

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 ( D rug R epurposing E ffort A pplying Integrated M odeling- in vitro/vivo - C linical D ata M ining), 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.