Examples of proposed allosteric modulator classifications
| Target Class | Target | Ligand | Proposed Ligand Descriptors |
|---|---|---|---|
| GPCR | Cannabinoid CB1 receptor | Org27569 | Org27569 is a PAM of CP55940 affinity but a NAM of CP55940 efficacy for mediating inhibition of cAMP accumulation. |
| GPCR | mGlu1 receptor | CPCCOEt | CPCCOEt is a NAL with respect to glutamate affinity but a NAM of glutamate efficacy in mediating intracellular calcium mobilization |
| GPCR | mGlu5 receptor | M-5MPEP | M-5MPEP is a NAL with respect to glutamate affinity and NAM of glutamate efficacy for stimulation of intracellular calcium mobilization and inositol phosphate accumulation |
| GPCR | CCR5 | Aplaviroc | Aplaviroc is a NAM of CCL3 affinity and a NAL with respect to CCL5 affinity; it is also a NAM of CCL3 and CCL5 efficacy to stimulate intracellular calcium mobilization. |
| LGIC | Benzodiazepine-sensitive GABAA receptors | Diazepam | Diazepam is a PAM of GABA affinity and chloride flux at benzodiazepine-sensitive GABAA receptors. |
| LGIC | GABAA receptor | Flumazenil | Flumazenil is a NAL with respect to GABA affinity and chloride flux at (most) GABAA receptor subtypes. |
| LGIC | GABAA receptor | Pentobarbital | Pentobarbital is a PAM of GABA affinity and chloride flux and an allosteric agonist with respect to GABAA receptor gating. |
| LGIC | nAChR | Lidocaine | Lidocaine is a PAM of acetylcholine affinity but a NAM of acetylcholine-mediated cation flux at the nAChR. |
| LGIC | NMDA (GluN1/GluN2A) | TCN-201 | TCN-201 is a NAM of glycine affinity and efficacy but a NAL of glutamate activity at the NMDA receptor. |
| VGIC | CaV1 | BayK8644 | BayK8644 is an allosteric agonist at CaV1 channels, a competitive antagonist of other dihydropyridines, a PAM with respect to diltiazem, and a NAM with respect to verapamil. |
| RTK | FGFR1 | SSR128129E | SSR128129E is NAL with respect to FGF2 affinity but a NAM of FGF2 efficacy to mediate phosphorylation of FRS2 and ERK1/2. It is a Type 3 tyrosine kinase inhibitor with respect to the ATP binding site. |
BayK8644, methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate; ERK1/2, extracellular signal-regulated kinase 1/2; FGFR1, FGF receptor 1; FRS2, fibroblast growth factor receptor substrate 2; M-5MPEP, 2-[(3-methoxyphenyl)ethynyl]-5-methylpyridine; NAL, neutral allosteric ligand (see also Note 10).