ABSTRACT
The inhibitor for the homophilic dimerization of P-cadherin was discovered by SPR-based screening using fragment compounds. Our SPR assays identified a specific P-cadherin binder, which was able to inhibit the cell adhesion of living CHO cells that expressed P-cadherin.
Subject(s)
Cadherins/antagonists & inhibitors , Cell Adhesion/drug effects , Isonicotinic Acids/pharmacology , Nicotinic Acids/pharmacology , Animals , Biological Assay , CHO Cells , Cadherins/immunology , Cell Aggregation/drug effects , Cricetulus , Dimerization , Immunoassay , Protein Multimerization , Single-Chain Antibodies/immunology , Surface Plasmon ResonanceABSTRACT
Fragment-based drug discovery (FBDD) has enjoyed increasing popularity in recent years. We introduce SITE (single-injection thermal extinction), a novel thermodynamic methodology that selects high-quality hits early in FBDD. SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources. We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency.
