Table 4.
Solved GPCR structures complexed with synthetic allosteric modulators bound to the intracellular surface
| Structure Type | GPCR type | GPCR | Modulator | Highest Phase | Modulator type | Number | PDB code | Allosteric site | Refs |
|---|---|---|---|---|---|---|---|---|---|
| Cryo-EM | class A | GPR88 | 2-PCCA | Pre-clinical | Allosteric agonist | (64) | 7EJX | outside 7TMD (V−VII) | 472 |
| X-ray diffraction | class B | GCGR | MK-0893 | Phase 2 | Allosteric antagonist | (65) | 5EE7 | outside 7TMD (V−VII) | 363 |
| X-ray diffraction | class B | GCGR | NNC0640 | Pre-clinical | NAM | (66) | 5XEZ | outside 7TMD (V−VII) | 364 |
| X-ray diffraction | class B | GLP-1R | NNC0640 | Pre-clinical | NAM | (66) | 5VEX | outside 7TMD (V−VII) | 365 |
| X-ray diffraction | class B | GLP-1R | PF-06372222 | Pre-clinical | NAM | (67) | 5VEW | outside 7TMD (V−VII) | 365 |
| Cryo-EM | class B | GLP-1R | compound 2 | Pre-clinical | ago-PAM | (68) | 7EVM | outside 7TMD (V−VII) | 358 |
| Cryo-EM | class C | GABAB | GS39783 | Pre-clinical | PAM | (69) | 6UO8 | outside 7TMD (V−VII) | 352 |
| Cryo-EM | class C | GABAB | BHFF | Pre-clinical | ago-PAM | (70) | 7C7Q | outside 7TMD (V−VII) | 351 |
| X-ray diffraction | class A | β2AR | Cmp-15PA | Pre-clinical | Allosteric antagonist | (71) | 5X7D | inside 7TMD | 473 |
| X-ray diffraction | class A | CCR2 | CCR2-RA-[R] | Pre-clinical | Allosteric antagonist | (72) | 5T1A | inside 7TMD | 474 |
| X-ray diffraction | class A | CCR9 | vercirnon | Phase 3 | Allosteric antagonist | (73) | 5LWE | inside 7TMD | 385 |
| X-ray diffraction | class A | CCR7 | Cmp2105 | Pre-clinical | Allosteric antagonist | (74) | 6QZH | inside 7TMD | 475 |
| X-ray diffraction | class A | CXCR2 | 00767013 | Pre-clinical | Allosteric antagonist | (75) | 6LFL | inside 7TMD | 476 |
| Cryo-EM | class A | GPR61 | Compound 1 | Pre-clinical | Allosteric inverse agonist | (76) | 8TB7 | inside 7TMD | 477 |
| Cryo-EM | class A | NTSR1 | SBI-553 | Pre-clinical | PAM | (77) | 8JPB | inside 7TMD | 478 |