Table 1.
Solved GPCR structures complexed with synthetic allosteric modulators bound to the extracellular vestibule
| Structure Type | GPCR Type | GPCR | Modulator | Highest Phase | Modulator type | Number | PDB code | Allosteric site | Refs |
|---|---|---|---|---|---|---|---|---|---|
| Cryo-EM | Class B | GLP-1R | LSN3160440 | Pre-clinical | PAM | (14) | 6VCB | outside 7TMD (I-II) | 180 |
| Cryo-EM | class A | GPR101 | AA-14 | Pre-clinical | Allosteric agonist | (15) | 8W8S | outside 7TMD (II-III) | 201 |
| X-ray diffraction | Class A | CCR5 | maraviroc | Approved | Allosteric inverse agonist | (16) | 4MBS | inside 7TMD | 181 |
| X-ray diffraction | Class A | PAR2 | AZ8838 | Pre-clinical | Allosteric antagonist | (17) | 5NDD | inside 7TMD | 451 |
| X-ray diffraction | Class A | GPR52 | c17 | Pre-clinical | Allosteric agonist | (18) | 6LI0 | inside 7TMD | 452 |
| Cryo-EM | Class A | LHCGR | Org43553 | Pre-clinical | Allosteric agonist | (19) | 7FIH | inside 7TMD | 453 |
| X-ray diffraction | Class A | M2R | LY2119620 | Pre-clinical | PAM | (20) | 4MQT | inside 7TMD | 216 |
| Cryo-EM | Class A | M4R | LY2119620 | Pre-clinical | PAM | (20) | 7V68 | inside 7TMD | 217 |
| Cryo-EM | Class A | M4R | compound-110 | Pre-clinical | Allosteric agonist | (21) | 7V6A | inside 7TMD | 217 |
| Cryo-EM | Class A | M4R | LY2033298 | Pre-clinical | PAM | (22) | 7TRP | inside 7TMD | 454 |
| Cryo-EM | Class A | M4R | VU0467154 | Pre-clinical | PAM | (23) | 7TRQ | inside 7TMD | 454 |
| Cryo-EM | Class A | TSHR | ML109 | Pre-clinical | Allosteric agonist | (24) | 7XW6 | inside 7TMD | 455 |
| Cryo-EM | Class A | MRGPRX1 | ML382 | Pre-clinical | PAM | (25) | 8DWG | inside 7TMD | 456 |
| X-ray diffraction | Class C | mGluR1 | FITM | Pre-clinical | NAM | (26) | 4OR2 | inside 7TMD | 457 |
| Cryo-EM | Class C | CaSR | cinacalcet | Approved | PAM | (27) | 7M3F | inside 7TMD | 230 |
| Cryo-EM | Class C | CaSR | evocalcet | Approved | PAM | (28) | 7M3G | inside 7TMD | 230 |
| Cryo-EM | Class C | CaSR | NPS-2143 | Pre-clinical | NAM | (29) | 7DD5 | inside 7TMD | 458 |
| Cryo-EM | Class C | CaSR | R-568 | Pre-clinical | PAM | (30) | 7SIL | inside 7TMD | 459 |
| Cryo-EM | Class C | mGluR2 | JNJ-40411813 | Phase 2 | PAM | (31) | 7E9G | inside 7TMD | 460 |
| X-ray diffraction | Class C | mGluR2 | NAM563 | Pre-clinical | NAM | (32) | 7EPE | inside 7TMD | 461 |
| X-ray diffraction | Class C | mGluR2 | NAM597 | Pre-clinical | NAM | (33) | 7EPF | inside 7TMD | 461 |
| X-ray diffraction | Class F | SMO | vismodegib | Approved | Allosteric antagonist | (34) | 5L7I | inside 7TMD | 462 |