Binding thermodynamics as a tool to investigate the mechanisms of drug-receptor interactions: thermodynamics of cytoplasmic steroid/nuclear receptors in comparison with membrane receptors.

Article Details

Citation

Gilli P, Gilli G, Borea PA, Varani K, Scatturin A, Dalpiaz A

Binding thermodynamics as a tool to investigate the mechanisms of drug-receptor interactions: thermodynamics of cytoplasmic steroid/nuclear receptors in comparison with membrane receptors.

J Med Chem. 2005 Mar 24;48(6):2026-35.

PubMed ID
15771445 [ View in PubMed
]
Abstract

Drug-receptor binding thermodynamics has proved to be a valid tool for pharmacological and pharmaceutical characterization of molecular mechanisms of receptor-recognition phenomena. The large number of membrane receptors so far studied has led to the discovery of enthalpy-entropy compensation effects in drug-receptor binding and discrimination between agonists and antagonists by thermodynamic methods. Since a single thermodynamic study on cytoplasmic receptors was known, this paper reports on binding thermodynamics of estradiol, ORG2058, and R1881 bound to estrogen, progesterone, and androgen steroid/nuclear receptors, respectively, as determined by variable-temperature binding constant measurements. The binding at 25 degrees C appears enthalpy/entropy-driven (-53.0

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CaffeineAdenosine receptor A1Kd (nM)45000N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)0.52N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)0.74N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)0.68N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)1.21N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)0.61N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)0.56N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)1.95N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)1.51N/AN/ADetails
MetriboloneAndrogen receptorKd (nM)0.99N/AN/ADetails
TheophyllineAdenosine receptor A1Kd (nM)12000N/AN/ADetails