sn003 and 4-(3-pentylamino)-2-7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1-5-a)pyrimidine

sn003 has been researched along with 4-(3-pentylamino)-2-7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1-5-a)pyrimidine* in 1 studies

Other Studies

1 other study(ies) available for sn003 and 4-(3-pentylamino)-2-7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1-5-a)pyrimidine

Article	Year
Quantitative pharmacological analysis of antagonist binding kinetics at CRF1 receptors in vitro and in vivo. British journal of pharmacology, 2011, Volume: 164, Issue:3 A series of novel non-peptide corticotropin releasing factor type-1 receptor (CRF(1)) antagonists were found to display varying degrees of insurmountable and non-competitive behaviour in functional in vitro assays. We describe how we attempted to relate this behaviour to ligand receptor-binding kinetics in a quantitative manner and how this resulted in the development and implementation of an efficient pharmacological screening method based on principles described by Motulsky and Mahan.. A non-equilibrium binding kinetic assay was developed to determine the receptor binding kinetics of non-peptide CRF(1) antagonists. Nonlinear, mixed-effects modelling was used to obtain estimates of the compounds association and dissociation rates. We present an integrated pharmacokinetic-pharmacodynamic (PKPD) approach, whereby the time course of in vivo CRF(1) receptor binding of novel compounds can be predicted on the basis of in vitro assays.. The non-competitive antagonist behaviour appeared to be correlated to the CRF(1) receptor off-rate kinetics. The integrated PKPD model suggested that, at least in a qualitative manner, the in vitro assay can be used to triage and select compounds for further in vivo investigations.. This study provides evidence for a link between ligand offset kinetics and insurmountable/non-competitive antagonism at the CRF(1) receptor. The exact molecular pharmacological nature of this association remains to be determined. In addition, we have developed a quantitative framework to study and integrate in vitro and in vivo receptor binding kinetic behaviour of CRF(1) receptor antagonists in an efficient manner in a drug discovery setting. Topics: Animals; Binding, Competitive; Cells, Cultured; CHO Cells; Cricetinae; Drug Discovery; Kinetics; Ligands; Male; Nonlinear Dynamics; Protein Binding; Pyrazoles; Pyridines; Pyrimidines; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Triazoles	2011

Article

Year

Quantitative pharmacological analysis of antagonist binding kinetics at CRF1 receptors in vitro and in vivo.

British journal of pharmacology, 2011, Volume: 164, Issue:3

A series of novel non-peptide corticotropin releasing factor type-1 receptor (CRF(1)) antagonists were found to display varying degrees of insurmountable and non-competitive behaviour in functional in vitro assays. We describe how we attempted to relate this behaviour to ligand receptor-binding kinetics in a quantitative manner and how this resulted in the development and implementation of an efficient pharmacological screening method based on principles described by Motulsky and Mahan.. A non-equilibrium binding kinetic assay was developed to determine the receptor binding kinetics of non-peptide CRF(1) antagonists. Nonlinear, mixed-effects modelling was used to obtain estimates of the compounds association and dissociation rates. We present an integrated pharmacokinetic-pharmacodynamic (PKPD) approach, whereby the time course of in vivo CRF(1) receptor binding of novel compounds can be predicted on the basis of in vitro assays.. The non-competitive antagonist behaviour appeared to be correlated to the CRF(1) receptor off-rate kinetics. The integrated PKPD model suggested that, at least in a qualitative manner, the in vitro assay can be used to triage and select compounds for further in vivo investigations.. This study provides evidence for a link between ligand offset kinetics and insurmountable/non-competitive antagonism at the CRF(1) receptor. The exact molecular pharmacological nature of this association remains to be determined. In addition, we have developed a quantitative framework to study and integrate in vitro and in vivo receptor binding kinetic behaviour of CRF(1) receptor antagonists in an efficient manner in a drug discovery setting.

Topics: Animals; Binding, Competitive; Cells, Cultured; CHO Cells; Cricetinae; Drug Discovery; Kinetics; Ligands; Male; Nonlinear Dynamics; Protein Binding; Pyrazoles; Pyridines; Pyrimidines; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Triazoles

2011