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Updated: Jul 19, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

Fragment-based lead discovery: a chemical update.

Daniel A Erlanson¹

¹Sunesis Pharmaceuticals, Inc., 341 Oyster Point Boulevard, South San Francisco, CA 94080, USA. erlanson@sunesis.com

Current Opinion in Biotechnology

|November 7, 2006

Summary

Fragment-based lead discovery uses small molecules to create drug leads efficiently. While successful, optimizing binding affinity during fragment linking and improvement remains a challenge.

Area of Science:

Drug discovery and medicinal chemistry
Chemical biology and structural biology

Background:

Fragment-based lead discovery (FBLD) is a popular drug discovery approach.
It constructs drug leads by assembling small molecular fragments.
FBLD has gained significant traction in recent years due to its potential efficiency.

Purpose of the Study:

To review various methods used in fragment-based lead discovery.
To highlight how different techniques have successfully generated drug leads.
To discuss challenges in maintaining molecular binding affinities during lead optimization.

Main Methods:

Nuclear Magnetic Resonance (NMR) spectroscopy
X-ray crystallography
Mass spectrometry

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Functional screening assays

In silico (computational) screening

Main Results:

Fragment-based lead discovery has reliably generated potent drug molecules.
Diverse screening approaches have been successfully employed.
Examples demonstrate the generation of viable drug leads from molecular fragments.

Conclusions:

Fragment-based lead discovery is a proven method for generating potent molecules.
Further research is needed to optimize binding affinities as fragments are elaborated.
Maintaining efficiency during fragment linking and improvement is crucial for FBLD success.