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Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
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Rapid lead discovery through iterative screening of one bead one compound libraries
Yu Gao1, Sabrina Amar, Sonia Pahwa
1Departments of Chemistry and Cancer Biology The Scripps Research Institute m 130 Scripps Way, Jupiter, Florida 33458, United States.
ACS Combinatorial Science
|December 2, 2014
Summary
Improving drug discovery hits is crucial. This study presents a workflow using binding constants and structure-activity relationship data to efficiently design and screen derivative libraries for enhanced compound potency against targets like matrix metalloproteinase-14.
Area of Science:
- Medicinal Chemistry
- Drug Discovery
- Biochemistry
Background:
- Primary hits from one bead one compound (OBOC) screening often lack high potency.
- Efficient workflows for improving these initial hits are underdeveloped.
Purpose of the Study:
- To establish an efficient workflow for primary hit improvement in drug discovery.
- To demonstrate rapid enhancement of a matrix metalloproteinase-14 inhibitor.
Main Methods:
- Characterizing binding constants for all primary screening hits.
- Generating structure-activity relationship (SAR) data from binding constants.
- Designing and screening derivative libraries based on SAR data under stringent conditions.
Main Results:
- The study successfully obtained SAR data from characterized binding constants.
- Derivative libraries were designed and screened, leading to improved compounds.
- Rapid improvement of a primary hit against matrix metalloproteinase-14 was achieved.
Conclusions:
- Characterizing binding constants is key to obtaining SAR data for hit improvement.
- This workflow enables efficient design and screening of derivative libraries for enhanced potency.
- The demonstrated approach accelerates the development of potent drug candidates.
