Orthosteric ligand

Allosteric modulators possess properties different from orthosteric ligands. Specifically, allosteric effects are saturable and probe dependent (i.e., the modulator produces different effects for different probes). 

Orthosteric antagonists, 131 Orthosteric ligands, 134t Osier, Sir William, 6 Outliers, 237-239, 252... 

FIGURE 3.7 Plots of fractional orthosteric Ugand-receptor occupancy as a function of log [orthosteric ligand concentration]. Curves shifts induced by a competitive antagonist (a) or a negative allosteric modulator (b). Note the limits in curve shifts with an allosteric modulator (ceiling effect). 

Muscarinic acetylcholine receptors (mAChRs) belong to the G protein-coupled receptor (GPCR) family. To date, five distinct subtypes of mAChRs (M1-M5) have been cloned and seqnenced. They share common orthosteric ligand-binding sites... 

Orthosteric ligands bind to the chemokine binding site and consequendy impair chemokine function through steric hindrance. In contrast, allosteric... 

Table 1 Unique Characteristics or Orthosteric Orthosteric Ligands...

Since it is known that different areas of the cytosolic loops of receptors activate different G proteins [191], it is evident that agonists can stabilize multiple active receptor conformations, thus changing not only the degree, but also the quality of receptor activation [192]. Consequently, three-state to multistate models have been developed. Furthermore, in thermodynamic terms must be a provision for the inactive receptor to also interact with G proteins, which lead to a more complex model for GPCRs, named the cubic ternary complex model [193]. Taking into account the concomitant binding of an orthosteric ligand led to a thermodynamically complete, extended model, named the quaternary complex model [194]. The above mentioned and additional models have been recently reviewed by Maudsley et al. [192], Kenakin et al. [195] and Christopoulos et al. [196]. Therein, the potential for allosteric... 

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