TABLE 5

Representative adenosine receptor modulators in clinical trials, currently and previously, according to clinicaltrials.gov

CompoundActionActivityPhase, National Clinical Trial Number
Agonists
Adenosine (1)Nonselective agonistheadache/migraine
ADCY5-related dyskinesia		-, 04577443
-, 04469283
Neladenoson bialanate
(77, BAY1067197)		A1AR agonistheart failure2, 02040233, PARSiFAL
2, 02992288, PANTHEON
2, 03098979, PANACHE
Selodenoson (78, DTI-0009, RG14202)A1AR agonistatrial fibrillation2, 00040001
Trabodenoson (79, INO-8875; PJ-875)A1AR agonistglaucoma3, 02565173
Regadenoson (2, CVT 3146)A2AAR agonistsickle cell anemia
COVID-19
pulmonary hypertension
glioma (disrupting BBB)		2, 01788631
1/2, 0460609
-, 02220634
1, 03971734
Tecadenoson (80, CVT-510)A2AAR agonistatrial fibrillation2, 00713401
Spongosine (81, BVT.115959)A2AAR agonistdiabetic nerve pain2, 00452777
UK-432,097 (11)A2AAR agonistchronic obstructive pulmonary disease2, 00430300
Piclodenoson (48, IB-MECA, CF-101)A3AR agonistrheumatoid arthritis
psoriasis
COVID-19		3, 02647762
3, 03168256
2, 04333472
Namodenoson
(14, Cl-IB-MECA, CF-102)		A3AR agonisthepatocellular carcinoma
NASH (non-alcoholic steatohepatitis)		2, 02128958
2, 02927314
Antagonists
Caffeine (3)Nonselective antagonisthypoxic-ischemic encephalopathy
ADCY5-related dyskinesia
Alzheimer’s disease
radiation-induced fibrosis
glaucoma		1, 03913221
-, 04469283
3, 04570085
2, 03768492
-, 03675412
Theophylline (4)
Nonselective antagonistacute kidney injury
smell in COVID-19
depression
anaesthesia recovery		3, 03897335
2, 04789499
1, 04309877
1, 04151381
Rolofylline (82, KW-3902)A1AR antagonistcongestive heart failure3, 00328692 (PROTECT-1)
3, 00354458 (PROTECT-2)
SLV320 (19)A1AR antagonistheart failure and
renal dysfunction
combined with furosemide		2, 00744341
2, 00160134
-, 00568009a
PBF-680A1AR antagonistasthma2, 03774290, ADENOASMA
Istradefylline (5, KW-6002)A2AAR antagonistParkinson’s disease (alone)2, 00250393
Parkinson’s disease (with l-dopa)3, 00955526, 6002-009
3, 01968031
Preladenant
(21, MK-3814, SCH 420814)
A2AAR antagonistParkinson’s disease3, 01155479, PARADYSE
antipsychotic drug side effects2, 00686699, P04628
advanced solid tumors (alone and in combination with pembrolizumab)1, 0309916
BIIB014 (65)A2AAR antagonistParkinson’s disease2, NCT00438607
Tozadenant (66)A2AAR antagonistParkinson’s disease3, NCT03051607
Taminadenant (83, NIR178, PBF-509)A2AAR antagonistParkinson’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 antagonistadvanced 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 antagonistcancer, alone1, 03980821
(in combination with CD73 blocker, MEDI9447d)1/2, 03381274
(in combination with anticancer drugs)1, 02740985
2, 04089553
Inupadenant (85, EOS100850) A2AAR antagonistsolid tumors1, 03873883
Etrumadenant (86, AB928)A2A/A2B antagonistvarious cancers (with AB122b)
(in combination with anticancer drugs)		1, 03629756
1/2, 04381832
PBF-1129A2BAR antagonistnon-small cell lung cancer1, 03274479
PBF-677A3AR antagonistglaucoma
ulcerative colitis		1, 02639975
2, 03773952, ADENOIBD
PBF-1650A3AR antagonistpsoriasis, NASH1, 03798236, ADENOIMMUNE
FM101 (87)A3AR antag/part agonistglaucoma
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.