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Updated: Oct 4, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
From hit to lead. Combining two complementary methods for focused library design. Application to mu opiate ligands
R Poulain1, D Horvath, B Bonnet
1Department of Chemistry, CEREP, 1 rue du Pr. Calmette, F-59000 Lille, France. rpoulain@phare.univ-lille2.fr
Abstract:
Compound 1 obtained by random screening and displaying a micromolar activity on the mu opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.
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