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Updated: May 25, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
Can we discover pharmacological promiscuity early in the drug discovery process?
Jens-Uwe Peters1, Jérôme Hert, Caterina Bissantz
1F Hoffmann-La Roche Ltd, pRED, Pharma Research & Early Development, Discovery Chemistry, CH-4070 Basel, Switzerland. jens-uwe.peters@roche.com
Abstract:
The term 'pharmacological promiscuity' describes the activity of a single compound against multiple targets. When undesired, promiscuity is a major safety concern that needs to be detected as early as possible in the drug discovery process. The analysis of large datasets reveals that the majority of promiscuous compounds are characterized by recognizable molecular properties and structural motifs, the most important one being a basic center with a pK(a)(B)>6. These compounds interact with a small set of targets such as aminergic GPCRs; some of these targets attract surprisingly high hit rates. In this review, we discuss current trends in the assessment of pharmacological promiscuity and propose strategies to enable early detection and mitigation.
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