Abstract K+/Cl- cotransporter 2 (KCC2) is selectively expressed in the adult nervous system and allows neurons to maintain low intracellular Cl- levels. Thus, KCC2 activity is an essential prerequisite for fast hyperpolarizing synaptic inhibition mediated by type A γ-aminobutyric acid (GABAA) receptors, which are Cl--permeable, ligand-gated ion channels. Consistent with this, deficits in the activity of KCC2 [...]
The small molecule CLP257 does not modify activity of the K+/Cl- co-transporter KCC2 but does potentiate GABA A receptor activity.
Read more here: RA Cardarelli, K Jones, LI Pisella, HJ Wobst, LJ McWilliams, PM Sharpe, MP Burnham, DJ Baker, I Chudotvorova, J Guyot, L Silayeva, DH Morrow, N Dekker, S Zicha, PA Davies, J Holenz, ME Duggan, J Dunlop, RJ Mather, Q Wang, I Medina, NJ Brandon, TZ Deeb and SJ Moss. The small molecule CLP257 [...]
A Screening Assay Cascade to Identify and Characterize Novel Selective Estrogen Receptor Downregulators (SERD’s).
Abstract Here, we describe an approach to identify novel selective estrogen receptor downregulator (SERD) compounds with improved properties such as oral bioavailability and the potential of increased efficacy compared to currently marketed drug treatments. Previously, methodologies such as Western blotting and transient cell reporter assays have been used to identify and characterize SERD compounds, but [...]