Rewiring Drug Research and Development through Human Data-Driven Discovery (HD3)

被引:1
作者
Jackson, David B. [1 ]
Racz, Rebecca [2 ]
Kim, Sarah [3 ]
Brock, Stephan [1 ]
Burkhart, Keith [2 ]
机构
[1] Mol Hlth GmbH, D-69115 Heidelberg, Germany
[2] US FDA, Div Appl Regulatory Sci, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA
[3] Univ Florida, Coll Pharm, Ctr Pharmacometr & Syst Pharmacol, Dept Pharmaceut, Orlando, FL 32827 USA
关键词
systems pharmacology; polypharmacology; adverse events; drug discovery; functional genomics; disease modeling; network analysis; innovation; ANIMAL-MODELS; TARGET; PROPRANOLOL; IMPACT; GENES; CELL;
D O I
10.3390/pharmaceutics15061673
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In an era of unparalleled technical advancement, the pharmaceutical industry is struggling to transform data into increased research and development efficiency, and, as a corollary, new drugs for patients. Here, we briefly review some of the commonly discussed issues around this counterintuitive innovation crisis. Looking at both industry- and science-related factors, we posit that traditional preclinical research is front-loading the development pipeline with data and drug candidates that are unlikely to succeed in patients. Applying a first principles analysis, we highlight the critical culprits and provide suggestions as to how these issues can be rectified through the pursuit of a Human Data-driven Discovery (HD3) paradigm. Consistent with other examples of disruptive innovation, we propose that new levels of success are not dependent on new inventions, but rather on the strategic integration of existing data and technology assets. In support of these suggestions, we highlight the power of HD3, through recently published proof-of-concept applications in the areas of drug safety analysis and prediction, drug repositioning, the rational design of combination therapies and the global response to the COVID-19 pandemic. We conclude that innovators must play a key role in expediting the path to a largely human-focused, systems-based approach to drug discovery and research.
引用
收藏
页数:25
相关论文
共 101 条
[11]  
Bohacek RS, 1996, MED RES REV, V16, P3, DOI 10.1002/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.3.CO
[12]  
2-D
[13]   Fragment-based drug discovery-the importance of high-quality molecule libraries [J].
Bon, Marta ;
Bilsland, Alan ;
Bower, Justin ;
McAulay, Kirsten .
MOLECULAR ONCOLOGY, 2022, 16 (21) :3761-3777
[14]  
Brock Stephan, 2022, Front Mol Med, V2, P1035215, DOI 10.3389/fmmed.2022.1035215
[15]  
Brock Stephan, 2022, Front Mol Med, V2, P1035290, DOI 10.3389/fmmed.2022.1035290
[16]   Bcr-Abl Tyrosine Kinase Inhibitors in the Treatment of Pediatric CML [J].
Carofiglio, Francesca ;
Lopalco, Antonio ;
Lopedota, Angela ;
Cutrignelli, Annalisa ;
Nicolotti, Orazio ;
Denora, Nunzio ;
Stefanachi, Angela ;
Leonetti, Francesco .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (12) :1-21
[17]  
centerwatch, TUFTS CTR REP TRIAL
[18]   Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference [J].
Cheng, Feixiong ;
Liu, Chuang ;
Jiang, Jing ;
Lu, Weiqiang ;
Li, Weihua ;
Liu, Guixia ;
Zhou, Weixing ;
Huang, Jin ;
Tang, Yun .
PLOS COMPUTATIONAL BIOLOGY, 2012, 8 (05)
[19]   The anti-cancer effects of itraconazole in epithelial ovarian cancer [J].
Choi, Chel Hun ;
Ryu, Ji-Yoon ;
Cho, Young-Jae ;
Jeon, Hye-Kyung ;
Choi, Jung-Joo ;
Ylaya, Kris ;
Lee, Yoo-Young ;
Kim, Tae-Joong ;
Chung, Joon-Yong ;
Hewitt, Stephen M. ;
Kim, Byoung-Gie ;
Bae, Duk-Soo ;
Lee, Jeong-Won .
SCIENTIFIC REPORTS, 2017, 7
[20]  
clarivate, OFF X PLATF