It was expected that destabilizing the C1B clamp would promote its disengagement from the NFD helix and the rest of the catalytic domain, lowering the energy barrier for translocation, and therefore lowering EC50 (PMA). Changing the register of the AGC linker in the cleft of the C1B domain,...
Results: We identified an AT1R allosteric compound that reduced AngII-mediated calcium signaling with a 5-fold shift in EC50. The IC50 was determined to be 18 M. It reduces the AngII-mediated vasoconstriction while blocking both monoclonal and patient-derived autoantibody binding with an IC50 of ...
The EC50 values are given in log and nm/μm. Fmut indicates the fold-increase for the ligand potencies in CCR5-CCR2(all) as compared with the WT receptor. The EC50 values of the chemokines are compared with those from CCR2, and the EC50 values of the metal ion chelators are ...
Consistent with its effect in cell lines, the mGluR5 PAM, VU-29 had no effect on baseline PI hydrolysis but induced a leftward shift in the DHPG concentration response curve (CRC) and enhanced the maximum response to DHPG (Figure 1a; DHPG alone, EC50=8±1.6 μM; DHPG+VU-29, EC50=...
an antagonist does not affect the equilibrium constant between the active and inactive states, binding equally to both forms. The antagonist prevents the agonist from binding to the orthosteric site and does not shift the equilibrium toward the activated receptor. Some receptors exhibit intrinsic activi...
VU-29 had no effect on baseline PI hydrolysis but induced a leftward shift in the DHPG concentration response curve (CRC) and enhanced the maximum response to DHPG (Figure 1a; DHPG alone, EC50 ¼ 8±1.6 mM; DHPG + VU-29, EC50 ¼ 4.5±1 mM, max response ¼ 138±12%, n ¼...
to the inactive state structure (Fig.1C). On the extracellular side, the major conformational changes include an inward shift of TM5 and TM7 in the active state structure compared with the changes in the inactive state structure. Although the static, active, and inactive states of AT1receptor...
Peak and steady-state (SS) dose-response relationships to glutamate were unchanged by lectin treatment (e.g. control, EC50(SS) = 31 +/- 28 microM vs Con-A, EC50(SS) = 45 +/- 9 microM, n = 6), suggesting that Con-A does not convert non-conducting channels with high agonist ...
Thislocalized backbone shift was consistent with key SAR results and wassubsequently confirmed by X-ray crystallography. The MD protocol guidedthe design of inhibitors, exploiting novel H-bond interactions withthe two backbone carbonyl groups, leading to the first thumb pocket2 NS5B inhibitor with ...
There is a dextral shift of the curve and an increase of the EC50 in the presence of octadienal (from 91 to 124 μM; inset: graphs as per A and B), expected when both compounds compete for the same binding site. Enhanced ORco inhibition by antagonist blends: additive or synergistic ...