Comprehensive Analysis of Clinically Discontinued Compounds Using an In Vitro Secondary Pharmacology Panel to Predict Potential Safety Risks during Drug Development
Summary
In vitro secondary pharmacology remains a critical tool in pharmaceutical drug discovery for evaluating potential off-target interactions before lead candidates advance into clinical development. Its primary aim is to reduce clinical attrition caused by adverse drug reactions and enhance patient safety. A widely adopted approach involves safety pharmacological profiling across a broad panel of targets, typically focusing on a chemical series with an identified therapeutic target. Utilizing a robust high-throughput screening platform, such as SAFETYscan47 from Eurofins Discovery, enables the rapid identification and mitigation of potential liabilities within discovery compounds. This article highlights the utility of in vitro pharmacological profiling by comparing clinically failed drug candidates against a broader compound modality data set. By more thoroughly evaluating the data generated through SAFETYscan47, we aim to demonstrate how in vitro profiling can offer valuable insights during preclinical discovery, ultimately supporting patient safety and reducing clinical attrition. © 2025 The Authors. Published by American Chemical Society.
| Authors | Albert V, Skinner DE, Karnwal S, Guili LN, Vazquez M, Ledezma O, Shaffer R, Celniker A, De La Cruz A, Caliendo M, Hanna AM, Galdieri L, King AJ, Servant NB, Jahic M |
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| Journal | ACS pharmacology & translational science |
| Publication Date | 2025 Sep 12;8(9):3314-3333 |
| PubMed | 40969870 |
| PubMed Central | PMC12441832 |
| DOI | 10.1021/acsptsci.5c00452 |