RESUMO
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.
Assuntos
Caderinas/antagonistas & inibidores , Adesão Celular/efeitos dos fármacos , Ácidos Isonicotínicos/farmacologia , Ácidos Nicotínicos/farmacologia , Animais , Bioensaio , Células CHO , Caderinas/imunologia , Agregação Celular/efeitos dos fármacos , Cricetulus , Dimerização , Imunoensaio , Multimerização Proteica , Anticorpos de Cadeia Única/imunologia , Ressonância de Plasmônio de SuperfícieRESUMO
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.