Table 2.
Solved GPCR structures complexed with synthetic allosteric modulators bound to the transmembrane domain outside 7TMD
| Structure Type | GPCR type | GPCR | Modulator | Highest Phase | Modulator type | Number | PDB code | Allosteric site | Refs |
|---|---|---|---|---|---|---|---|---|---|
| X-ray diffraction | class A | P2Y1 | BPTU | Pre-clinical | Allosteric antagonist | (37) | 4XNV | outside 7TMD (I–III) | 242 |
| X-ray diffraction | class A | PAR2 | AZ3451 | Pre-clinical | Allosteric antagonist | (38) | 5NDZ | outside 7TMD (II–IV) | 451 |
| X-ray diffraction | class A | CB1R | ORG27569 | Pre-clinical | NAM | (39) | 6KQI | outside 7TMD (II–IV) | 257 |
| X-ray diffraction | class A | CB1R | ZCZ011 | Pre-clinical | PAM | (40) | 7FEE | outside 7TMD (II–IV) | 261 |
| X-ray diffraction | class A | GPR40 | compound 1 | Pre-clinical | Allosteric agonist | (41) | 5KW2 | outside 7TMD (III–V) | 463 |
| X-ray diffraction | class A | GPR40 | AP8 | Pre-clinical | AgoPAM | (42) | 5TZY | outside 7TMD (III–V) | 464 |
| X-ray diffraction | class A | β2AR | Cmpd-6FA | Pre-clinical | PAM | (43) | 6N48 | outside 7TMD (III–V) | 269 |
| X-ray diffraction | class A | β2AR | AS408 | Pre-clinical | NAM | (44) | 6OBA | outside 7TMD (III–V) | 465 |
| X-ray diffraction | class A | C5aR1 | NDT9513727 | Pre-clinical | Allosteric inverse agonist | (45) | 5O9H | outside 7TMD (III–V) | 466 |
| X-ray diffraction | class A | C5aR1 | avacopan | Approved | Allosteric antagonist | (46) | 6C1R | outside 7TMD (III–V) | 467 |
| Cryo-EM | class A | DRD1 | LY3154207 | Phase 2 | PAM | (47) | 7CKZ | outside 7TMD (III–V) | 277 |
| Cryo-EM | class A | CXCR3 | SCH546738 | Pre-clinical | Allosteric antagonist | (48) | 8HNN | outside 7TMD (V–VI) | 299 |
| Cryo-EM | class A | A1R | MIPS521 | Pre-clinical | PAM | (49) | 7LD3 | outside 7TMD (I, VI, VII) | 305 |
| Cryo-EM | class A | GPR101 | AA-14 | Pre-clinical | Allosteric agonist | (15) | 8W8S | outside 7TMD (I, VI, VII) | 201 |
| Cryo-EM | class C | mGlu4 | VU0364770 | Pre-clinical | PAM | (50) | 8JD5 | outside 7TMD (I, VI, VII) | 468 |
| Cryo-EM | class C | mGlu4 | ADX88178 | Pre-clinical | PAM | (51) | 8JD6 | outside 7TMD (I, VI, VII) | 468 |