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摘要
En 中文
Reverse translation (RT) refers to perceptions and observations of clinical outcomes, both beneficial and harmful, that can lead to a hypothesis intended to identify a new use of a drug that is different from the original use. I provide a panoramic view of successes in RT from the historic discovery of penicillin to the contemporary development of CAR (chimeric antigen receptor) T therapies. I delineate the core principles of RT that shift discovery from serendipity to a systematic strategy based on target identification and causal biology, pharmacodynamic biomarkers that recapitulate disease pathophysiology, confirmation of target engagement by clinical proof of concept studies, and optimal selection of dose and interval. The article proposes four different categories of RT and successful examples are provided for each category. It concludes with a summary of open questions related to the business case of RT that includes a comparison of the pros, cons, and barriers to future RT development programs.
Keyword:
ROSIGLITAZONE
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5.5
论文数:
8.6K
被引数:
1.9W
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