[¹²⁵I]YP20: a novel radioligand specific for the extracellular domain of the CRF₁ receptor.

The peptide corticotropin-releasing factor (CRF) binds to the CRF₁ receptor via a two-domain mechanism such that the extracellular domain (ECD) of the receptor captures the CRF's C-terminus to facilitate the binding of CRF's N-terminus to the juxta-membrane or "J"-site. Known small molecule antagonists bind to the J-site while known CRF₁ receptor peptide radioligands bind to both sites. We report here the in vitro binding properties of the first radioligand that binds exclusively to the ECD of the CRF₁ receptor.

In vitro binding characteristics of [3H]AZ11637326, a novel alpha7-selective neuronal nicotinic receptor agonist radioligand.

AZ11637326 (5'-(2-fluoro[3,4,5(-3)H3]phenyl)-spiro[1-azabicyclo [2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine) is a potent partial agonist at the human alpha7 neuronal nicotinic receptor with sub-nanomolar affinity for the human and rat alpha7 [(125)I]alpha-bungarotoxin binding sites.

Evaluation of cellular dielectric spectroscopy, a whole-cell, label-free technology for drug discovery on Gi-coupled GPCRs.

Cellular dielectric spectroscopy (CDS) is an emerging technology capable of detecting a range of whole-cell responses in a label-free manner. A new CDS-based instrument, CellKey, has been developed that is optimized for G-protein coupled receptor (GPCR) detection and has automated liquid handling in microplate format, thereby making CDS accessible to lead generation/optimization drug discovery. In addition to having sufficient throughput, new assay technologies must pass rigorous standards for assay development, signal window, dynamic range, and reproducibility to effectively support drug discovery SAR studies.