The earliest phases of drug discovery require diverse scientific disciplines to work hand in hand to address many unknowns. Good decision making is crucial for success in this context and, yet, the topic of sound planning has rarely been addressed for the earliest stages of drug discovery. We propose a tailored, qualitative 'decision quality' process that can serve as a guide toward generating project plans optimized to address a given project situation. Furthermore, we propose a visual flow-chart format for the selected plan that includes key decisions and activities, together forming a decision roadmap of the plan. We illustrate each step of the process by means of a real-life example and provide recommendations for its implementation.
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http://dx.doi.org/10.1016/j.drudis.2024.104016 | DOI Listing |
J Affect Disord
January 2025
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address:
Background And Objective: To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine.
Design: We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders.
Main Measures: Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR).
Ecotoxicol Environ Saf
January 2025
Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:
Di(2-ethylhexyl) phthalate (DEHP) is a widespread ubiquitous phthalate environmental contaminant. The male reproductive toxicity (MRT) from exposure to DEHP and its main metabolite, mono(2-ethylhexyl) phthalate (MEHP), has been well documented. Fully elucidating its toxic mechanism and discovering effective antagonists are desirable means to reduce the health risks of DEHP.
View Article and Find Full Text PDFEur J Med Chem
January 2025
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, #345 Lingling Rd, Shanghai, 200032, China. Electronic address:
The pseudokinase HER3 emerges as a promising anti-cancer target, especially for HER2-driven breast cancer and EGFR-mediated non-small cell lung cancer. However, it is challenging to target HER3 by ATP-competitive small molecules because HER3 is catalytically impaired. Herein, we report the discovery of a series of HER3 degraders by connecting a HER3 binder bosutinib with a hydrophobic tag adamantane.
View Article and Find Full Text PDFHepatology
January 2025
State Key Laboratory of Liver Research, Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
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