Computational integration and meta-analysis of abandoned cardio-(vascular/renal/metabolic) therapeutics discontinued during clinical trials from 2011 to 2022

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Bohdan B. Khomtchouk¹  Deniel Mero²  Austin Szatrowski³  Yoon Seo Lee³  Carisa Zeng³ 

[1] Department of BioHealth Informatics, Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, IN, United States;Krannert Cardiovascular Research Center, Indiana University School of Medicine, Indianapolis, IN, United States;Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, United States;Dock Therapeutics, Inc., Lewes, DE, United States;The College of the University of Chicago, Chicago, IL, United States;

关键词: cardioinformatics;    databases;    drug repurposing;    computation;    bioinformatics;   

DOI  :  10.3389/fcvm.2023.1033832

 received in 2022-09-01, accepted in 2023-01-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

Cardiovascular/renal/metabolic (CVRM) diseases collectively comprise the leading cause of death worldwide and disproportionally affect older demographics and historically underrepresented minority populations. Despite these critical unmet needs, pharmaceutical research and development (R&D) efforts have historically struggled with high drug failure rates, low approval rates, and other challenges. Drug repurposing is one approach to recovering R&D costs and meeting unmet demands in therapeutic markets. While there are multiple approaches to conducting drug repurposing, we recognize the importance of bringing together and consolidating discontinued drug information to help identify prospective repurposing candidates. In this study, we have harmonized and integrated information on all relevant CVRM drug assets from U.S. Securities and Exchange Commission (SEC) filings, clinical trial records, PharmGKB, Open Targets, and other platforms. A list of existing therapeutics discontinued or shelved by pharmaceutical/biotechnology companies in 2011–2022 were manually curated and interpreted for insights using information on each drug’s genetic target, mechanism of action (MOA), clinical indication, and R&D information including highest phase of clinical development, year of discontinuation, previous repurposing attempts (if any), and other actionable metadata. This study also summarizes the profiles of CVRM drugs discontinued within the past decade and identifies the limitations of publicly available information on discontinued drug assets. The constructed database could serve as a tool for identifying candidates for drug repurposing and developing query methods for collecting R&D information.

【 授权许可】

Unknown   
Copyright © 2023 Zeng, Lee, Szatrowski, Mero and Khomtchouk.