Affinity and kinetics study of anthranilic acids as HCA2 receptor agonists

A two‐state model for the kinetics of competitive radioligand binding

“…However, the application of the model is limited because of the assumption that the labelled reference ligand does not have preference for any particular receptor state, hence representing a one‐state model. A labelled probe, for example, a radioligand, may display biphasic kinetic binding, representing different binding kinetics to different receptor states (Munshi et al ., ; van Veldhoven et al ., ). A number of reasons may be relevant to the nature of the biphasic kinetic binding.…”

“…However, it is known that a radioligand may display biphasic binding characteristics to the receptor. For instance, an agonist radioligand often has a strong preference for a given state of a GPCR over another, thus resulting in a biphasic association (Munshi et al ., ; van Veldhoven et al ., ). In this situation, the one‐state model is no longer applicable for quantitative kinetic measurements.…”

Crystal structure of 3-(4-hydroxy-3-methoxyphenyl)-N-phenylpropanamide, C16H17NO3

“…3-Aryl-N-arylpropanamides rise interest both due to synthetic applications and wide range of biological activity (e. g., they act as antitubercular [3] and antibiotic [4] agents, as well as HCA2 receptor agonists [5]). These compounds serve as starting materials for synthesis of 3-arylpropanols [6], 1,3-diarylpropan-1-ones [7], quinolines [8], β-l lactams [9], 4-aryl-2-quinolinones [10] and 1-indanones [11], as well as ligands in iridium complexes [12].…”

Binding kinetics in drug discovery ndash A current perspective

“…Indirect binding kinetics assays monitor the association and dissociation of labeled ligands in the presence or absence of unlabeled test compounds. To this end, mainly two approaches have been described: either I) simultaneous competitive target binding of an unlabeled compound and a labelled tracer (77,86,88) or II) displacement of pre-bound tracer or unlabeled compound by the test compound or the labeled tracer, respectively (59,87,89,90). By using the binding kinetics parameters of the tracer (previously determined in direct binding experiments), the kinetic rate constants of the compound can be calculated based on appropriate mathematical models: Competitive binding allows for simultaneous determination of both, k on and k off using the competitive binding kinetics equations (91) whereas displacement assays solely enable k on and k off determinations via k obs or exponential decay models.…”

“…Radiolabeling is often the label of choice for lower throughput applications such as direct binding assays. However, -as stated above -there are also publications performing competition binding (86,88) and displacement (86)(87)(88) An alternative to the standard filtration assay is the scintillation proximity based assay SPA (113), a homogenous assay format in which light is emitted upon binding of the radioligand to the target immobilized on beads (containing the scintillant). In this way no scintillation cocktail and no separation step is required leading to reduced amounts of radioactive waste, higher throughput and improved kinetic resolution.…”