TABLE 5.
Representative adenosine receptor modulators in clinical trials, currently and previously, according to clinicaltrials.gov
| Compound | Action | Activity | Phase, National Clinical Trial Number |
|---|---|---|---|
| Agonists | |||
| Adenosine (1) | Nonselective agonist | headache/migraine ADCY5-related dyskinesia |
-, 04577443 -, 04469283 |
| Neladenoson bialanate (77, BAY1067197) |
A1AR agonist | heart failure | 2, 02040233, PARSiFAL 2, 02992288, PANTHEON 2, 03098979, PANACHE |
| Selodenoson (78, DTI-0009, RG14202) | A1AR agonist | atrial fibrillation | 2, 00040001 |
| Trabodenoson (79, INO-8875; PJ-875) | A1AR agonist | glaucoma | 3, 02565173 |
| Regadenoson (2, CVT 3146) | A2AAR agonist | sickle cell anemia COVID-19 pulmonary hypertension glioma (disrupting BBB) |
2, 01788631 1/2, 0460609 -, 02220634 1, 03971734 |
| Tecadenoson (80, CVT-510) | A2AAR agonist | atrial fibrillation | 2, 00713401 |
| Spongosine (81, BVT.115959) | A2AAR agonist | diabetic nerve pain | 2, 00452777 |
| UK-432,097 (11) | A2AAR agonist | chronic obstructive pulmonary disease | 2, 00430300 |
| Piclodenoson (48, IB-MECA, CF-101) | A3AR agonist | rheumatoid arthritis psoriasis COVID-19 |
3, 02647762 3, 03168256 2, 04333472 |
| Namodenoson (14, Cl-IB-MECA, CF-102) |
A3AR agonist | hepatocellular carcinoma NASH (non-alcoholic steatohepatitis) |
2, 02128958 2, 02927314 |
| Antagonists | |||
| Caffeine (3) | Nonselective antagonist | hypoxic-ischemic encephalopathy ADCY5-related dyskinesia Alzheimer’s disease radiation-induced fibrosis glaucoma |
1, 03913221 -, 04469283 3, 04570085 2, 03768492 -, 03675412 |
| Theophylline (4) |
Nonselective antagonist | acute kidney injury smell in COVID-19 depression anaesthesia recovery |
3, 03897335 2, 04789499 1, 04309877 1, 04151381 |
| Rolofylline (82, KW-3902) | A1AR antagonist | congestive heart failure | 3, 00328692 (PROTECT-1) 3, 00354458 (PROTECT-2) |
| SLV320 (19) | A1AR antagonist | heart failure and renal dysfunction combined with furosemide |
2, 00744341 2, 00160134 -, 00568009a |
| PBF-680 | A1AR antagonist | asthma | 2, 03774290, ADENOASMA |
| Istradefylline (5, KW-6002) | A2AAR antagonist | Parkinson’s disease (alone) | 2, 00250393 |
| Parkinson’s disease (with l-dopa) | 3, 00955526, 6002-009 3, 01968031 |
||
| Preladenant (21, MK-3814, SCH 420814) |
A2AAR antagonist | Parkinson’s disease | 3, 01155479, PARADYSE |
| antipsychotic drug side effects | 2, 00686699, P04628 | ||
| advanced solid tumors (alone and in combination with pembrolizumab) | 1, 0309916 | ||
| BIIB014 (65) | A2AAR antagonist | Parkinson’s disease | 2, NCT00438607 |
| Tozadenant (66) | A2AAR antagonist | Parkinson’s disease | 3, NCT03051607 |
| Taminadenant (83, NIR178, PBF-509) | A2AAR antagonist | Parkinson’s disease, non-small cell lung cancer (with PDR001b) | 1, 02111330 1/2, 02403193, AdenONCO |
| various cancersc (with PDR001) | 3, 03207867 | ||
| Ciforadenant (84, CPI-444, V81444) | A2AAR antagonist | advanced cancers (in combination with CD73 blocker, CPI-0006) | 1, 03454451 |
| (in combination with PD-L1/PD-1b) | 1/2, 03337698 | ||
| Imaradenant (22, AZD4635, HTL1071) | A2AAR antagonist | cancer, alone | 1, 03980821 |
| (in combination with CD73 blocker, MEDI9447d) | 1/2, 03381274 | ||
| (in combination with anticancer drugs) | 1, 02740985 2, 04089553 |
||
| Inupadenant (85, EOS100850) | A2AAR antagonist | solid tumors | 1, 03873883 |
| Etrumadenant (86, AB928) | A2A/A2B antagonist | various cancers (with AB122b) (in combination with anticancer drugs) |
1, 03629756 1/2, 04381832 |
| PBF-1129 | A2BAR antagonist | non-small cell lung cancer | 1, 03274479 |
| PBF-677 | A3AR antagonist | glaucoma ulcerative colitis |
1, 02639975 2, 03773952, ADENOIBD |
| PBF-1650 | A3AR antagonist | psoriasis, NASH | 1, 03798236, ADENOIMMUNE |
| FM101 (87) | A3AR antag/part agonist | glaucoma NASH |
1/2, 04585100 2, 04710524 |
Note that this list is not all-inclusive (e.g., dipyridamole has been omitted). Other compounds are reviewed elsewhere (Borah et al., 2019; Jacobson et al., 2019). Structures, when disclosed, are shown in Figs. 1, 2, 3, and 5.
aterminated additional enrollment criteria made patient recruitment unfeasible.
bcheckpoint inhibitor.
ctriple negative breast cancer, pancreatic ductal adenocarcinoma, non-small cell lung cancer, renal cell cancer, urothelial cancer, head and neck cancer, diffused large B cell lymphoma, microsatellite stable colon cancer, non-Hodgkin lymphoma.
doleclumab.