Table 6.
Drugs targeting GPCRs in clinical trials
| Targeted GPCR | Drug Name | Indications | Stage (Year) | Mechanism | References |
|---|---|---|---|---|---|
| Dopamine D2 Receptor (DRD2) | Chlorpromazine | Schizophrenia | Approved (1957) | D2 antagonist | 168 |
| β1/β2-Adrenergic Receptor (ADRB1/2) | Propranolol | Hypertension, Angina, Arrhythmias | Approved (1964) | β1/β2 antagonist | 169 |
| β2-Adrenergic Receptor (ADRB2) | Salbutamol | Acute Asthma | Approved (1969) | β2 agonist | 170 |
| H1 Receptor (HRH1) | Loratadine | Allergic Rhinitis | Approved (1993) | H1 antagonist | 171 |
| Calcium-Sensing Receptor (CaSR) | Cinacalcet | Hyperparathyroidism | Approved (2004) | CaSR positive allosteric modulator | 160 |
| S1P Receptor | Fingolimod | Multiple Sclerosis | Approved (2010) | S1P1 functional antagonist | 172 |
| GLP-1 Receptor (GLP1R) | Semaglutide | T2DM, Obesity | Approved (2017) | GLP-1R agonist | 173 |
| CGRP Receptor | Erenumab (Aimovig) | Migraine Prevention | Approved (2018) | CGRP receptor antagonist (mAb) | 174 |
| GPRC5D Receptor | Teclistamab | Relapsed/Refractory Multiple Myeloma | Approved (2022) | GPRC5D antagonist (bispecific antibody) | 175 |
| 5-HT1A Receptor (HTR1A) | Gepirone | Major Depressive Disorder | Approved (2023) | 5-HT1A partial agonist | 176 |
| Muscarinic M1/M4 Receptor (CHRM1/4) | KarXT (Xanomeline) | Schizophrenia | Approved (2024) | M1/M4 agonist, peripheral antagonist | 177 |
| EP4 Receptor (PTGER4) | YY001 (ECNU) | Advanced Solid Tumors | Phase II (2021) | EP4 antagonist | 178 |
| CCR8 Receptor | HBM1022 (Harbour BioMed) | Solid Tumors | Phase I (2023) | CCR8 antagonist (mAb) | 3 |
| PTH1 Receptor (PTH1R) | SEP-786 (Septerna) | Hypoparathyroidism | Phase II (2023) | PTH1R oral allosteric agonist | 166 |
| GLP-1R/GCGR/GIPR | Retatrutide (Lilly) | Obesity | Phase III (2024) | Triple agonist | 179 |
| ADGRG2 Receptor | Nb23-bi (SDU) | Orchitis/Neuroinflammation | Preclinical (2025) | Allosteric nanobody (w/DHEA) | 180 |