Table 1.
Therapeutic targets of the adenosine and hypoxia pathways and health conditions and diseases of current clinical trials
| Drug | Target | Phase | Condition | Indications | https://ClinicalTrials.gov Identifier (Status) |
|---|---|---|---|---|---|
| ATP | Phase 2 | Major depressive disorder | Antidepressant effect | NCT03138681 (recruiting) | |
| Acetogenins | ATP production inhibitor | Phase 2/Phase 3 | Breast cancer | Anti-proliferative, apoptosis effect | NCT02286778 (active, not recruiting) |
| Ticagrelor | P2Y12 antagonist | Phase 4 | Microvascular angina | Ameliorate coronary microvascular function | NCT02284048 (not yet recruiting) |
| Phase 4 | Migraine headache | Eliminate migraine headaches | NCT02518464 (recruiting) | ||
| Phase 3 | Acute ST-elevation myocardial infarction | Antiplatelet therapy | NCT01739556 (recruiting) | ||
| Phase 3 | Diabetes mellitus, Type 2 | Effect on cardiovascular death, myocardial infarction, or stroke | NCT01991795 (active, not recruiting) | ||
| Cangrelor | P2Y12 antagonist | Phase 1 | Partial obstruction of systemic to pulmonary artery shunt; complete obstruction of systemic to pulmonary artery shunt | Safety profile in neonatal participants at risk of thrombosis | NCT02765633 (recruiting) |
| Cangrelor; Ticagrelor | P2Y12 antagonist | Phase 4 | Acute coronary syndrome; microvascular obstruction; ST-segment elevation myocardial infarction; thrombolysis in myocardial infarction; unstable angina | Intravenous antiplatelet therapy | NCT02733341 (recruiting) |
| Clopidogrel; Ticagrelor | P2Y12 antagonist | Phase 4 | Coronary artery disease | Reduce later heart attacks | NCT02327624 (active, not recruiting) |
| Phase 4 | Patients who are scheduled to undergo a PCI (percutaneous coronary intervention) for CTO (chronic total occlusion) | Percutaneous coronary intervention and the recovery of vascular function at long-term | NCT02211066 (recruiting) | ||
| Phase 3 | Acute coronary syndrome | Prevention of fatal and nonfatal cardiovascular events, observation of coronary circulation effects due to chronic use | NCT02618733 (recruiting) | ||
| Phase 2 | Coronary artery disease; kidney dysfunction | Reducing ischemic events | NCT03039205 (not yet recruiting) | ||
| Phase 2 | Stroke; ischemic attack, transient | Combination with aspirin effect on reducing transient ischemic attack or minor stroke | NCT02506140 (recruiting) | ||
| Prasugrel; Ticagrelor | P2Y12 antagonist | Phase 4 | Acute coronary syndrome | Pleiotropic effects to antiplatelet therapy in type 2 diabetic patients with non-ST elevation acute coronary syndrome | NCT02487732 (active, not recruiting) |
| MEDI9447 with or without MEDI4736 | CD73 (MEDI9447); anti-PD-LI antibody (MEDI4736) | Phase 1 | Solid tumors | Safety profile in adult subjects with select advanced solid tumors (combat tumor immunosuppression) | NCT02503774 (recruiting) |
| Adenosine | Phase 2 | Cardiomyopathies | An adjunct to intermittent warm blood cardioplegia | NCT02681913 (recruiting) | |
| Phase 2 | Takotsubo cardiomyopathy; Takotsubo syndrome | Induce rapid recovery of left ventricle function | NCT02867878 (recruiting) | ||
| Phase 2/Phase 1 | Sinus bradycardia; atrioventricular block | Safety profile in children with heart transplant, effectiveness in treating fast heart rate | NCT02462941 (active, but not recruiting) | ||
| Neladenoson Bialanate (BAY 1067197) | A1AR agonist | Phase 2 | Heart failure | Optimal dose given in addition to standard therapy for heart failure | NCT02992288 (recruiting) |
| Regadenoson | A2AAR agonist | Phase 2 | Retinal artery occlusion | Induce vasodilatation in adjacent retinal areas to increase blood flow and retinal oxygenation | NCT03090087 (recruiting) |
| Phase 2 | Sickle cell anemia | Effective treatment for pain crises and acute chest syndrome in sickle cell disease | NCT01788631 (recruiting) | ||
| Phase 1 | Lung transplant | Ischemia reperfusion injury lowered or prevented. Regadenoson is an A2AAR drug | NCT03072589 (not yet recruiting) | ||
| Phase 1 | Blood-brain barrier defect | Transiently disrupt the blood-brain barrier, improve drug penetration | NCT02389738 (recruiting) | ||
| N/A | Sickle cell disease; sickle cell anemia | Prevent inflammation and injury caused by the sickle shaped cells | NCT01566890 (recruiting) | ||
| CF102 | A3AR agonist | Phase 2 | Nonalcoholic steatohepatitis | Safety and efficacy, improve liver pathology | NCT02927314 (not yet recruiting) |
| Phase 2 | Hepatocellular carcinoma | Efficacy and safety, tumor reduction, improved survival | NCT02128958 (recruiting) | ||
| Aminophylline | Nonselective adenosine receptor (AR) antagonist | Phase 1 | Premature obstetric labor | Combination with progesterone reduces the risk of preterm labor | NCT03152942 (not yet recruiting) |
| Phase 1 | Acute kidney injury | Mitigates this vasoconstriction, reduce ischemic kidney injury | NCT02983422 (not yet recruiting) | ||
| Vivarin (caffeine) | Nonselective AR antagonist | Phase 2/Phase 1 | Narcolepsy | Effects of caffeine consumption on daytime sleepiness and reaction time | NCT02832336 (recruiting) |
| Caffeine | Nonselective AR antagonist | Phase 2/Phase 1 | Pain | Assess caffeine on acupuncture analgesia | NCT02577770 (recruiting) |
| N/A | Schizophrenia | Improve cognitive function | NCT02832401 (not yet recruiting) | ||
| PBF-680 | A1AR antagonist | Phase 2 | Asthma | To attenuate “late asthmatic responses” as a primary efficacy outcome, assess airway inflammation-related outcomes | NCT02635945 (recruiting) |
| Phase 3 | Acute coronary syndrome | Prevention of fatal and nonfatal cardiovascular events, observation of coronary circulation effects due to chronic use | NCT02618733 (recruiting) | ||
| Istradefylline | A2AAR antagonist | Phase 3 | Idiopathic Parkinson’s disease | Safety and tolerability, nondopaminergic therapy | NCT02610231 (active, not recruiting) |
| Pentoxifylline | A2AAR antagonist | Phase 3 | Acute pancreatitis; gallstone pancreatitis; alcoholic pancreatitis; Post-ERCP/postprocedural pancreatitis; trauma acute pancreatitis; hypertriglyceridemia acute pancreatitis; idiopathic (unknown) acute pancreatitis; medication-induced acute pancreatitis; cancer acute pancreatitis; miscellaneous (i.e., acute or chronic pancreatitis) | Inhibition of the tumor necrosis factor-alpha pathway reduces inflammation | NCT02487225 (enrolling by invitation) |
| PBF-509 with or without PDR001 | A2AAR antagonist (PBF-509); anti-PD-1 antibody (PDR001) | Phase 2/Phase 1 | Non-small cell lung cancer (NSCLC) | Safety, tolerability, feasibility, and preliminary efficacy (combat tumor immunosuppression) | NCT02403193 (recruiting) |
| CPI-444 with or without atezolizumab | A2AAR antagonist (CPI-444); anti-PD-L1 antibody (atezolizumab) | Phase 1 | NSCLC; malignant melanoma; renal cell cancer; triple negative breast cancer; colorectal cancer; bladder cancer | Safety, tolerability, and anti-tumor activity (combat tumor immunosuppression) | NCT02655822 (recruiting) |
| EZN-2279; Adagen | Adenosine deaminase (ADA) | Phase 3 | ADA-SCID; adenosine deaminase deficiency; severe combined immunodeficiency | Safety, efficacy, and pharmacokinetics [enzyme (ADA) replacement therapy] | NCT01420627 (recruiting) |
| ADA gene transduced CD34+ cells | ADA | Phase 2 | Immunologic deficiency syndromes | Safety and the clinical efficacy of gene therapy (ADA), evaluate the immunological reconstitution and purine metabolism after gene therapy | NCT00598481 (active, not recruiting) |
| EF1αS-ADA | ADA | Phase 2/Phase 1 | Adenosine deaminase deficiency; severe combined immunodeficiencies (SCID) | Safety, feasibility, effectiveness of gene therapy for ADA-deficient SCID using lentiviral vector | NCT01380990 (recruiting) |
| EFS-ADA | ADA | Phase 2/Phase 1 | ADA-SCID | safety and effectiveness of using a lentiviral vector (based on HIV-1) for ADA-deficient SCID | NCT01852071 (active, not recruiting) |
| Pentostatin | ADA inhibitor | Phase 3 | Graft-vs.-host disease | Efficacy of ruxolitinib against best available therapy in participants with steroid-refractory chronic graft-vs.-host disease | NCT03112603 (recruiting) |
| Phase 2 | Renal cell carcinoma; Graft-vs.-Host disease; Engraftment Syndrome | Determine whether new, low-intensity transplant approach can yield objective partial or complete remission | NCT00923845 (active, not recruiting) | ||
| Phase 2 | Leukemia; lymphoma | Stop the growth of cancer cells, combination therapy | NCT00602836 (active, not recruiting) | ||
| Phase 2 | Acute lymphoblastic leukemia; acute myeloid leukemia; chronic lymphocytic leukemia; chronic myelogenous leukemia, BCR-ABL1 positive; graft vs. host disease; Hodgkin lymphoma; myelodysplastic/myeloproliferative neoplasm; non-Hodgkin’s lymphoma; plasma cell myeloma; Waldenstrom macroglobulinemia | Preventing graft rejection in patients who have undergone donor stem cell transplant | NCT00096161 (active, not recruiting) | ||
| Phase 2 | Hairy cell leukemia | Determine whether pentostatin or bendamustine is a more effective when combined with rituximab | NCT01059786 (recruiting) | ||
| Phase 2 | Graft-vs.-host disease | Effectiveness in treating chronic graft-vs.-host disease in patients refractory to treatment with steroids | NCT00074035 (active, not recruiting) | ||
| Phase 2/Phase 1 | Sickle cell disease | Novel immunosuppressive regimen without myeloablation to further decrease the transplant-related morbidity/mortality | NCT03077542 (recruiting) | ||
| Phase 2/Phase 1 | Sickle cell disease; thalassemia; stem cell transplantation; graft vs. host disease | Reduce the transplant failure rate | NCT02105766 (recruiting) | ||
| Phase 2/Phase 1 | Mesothelioma; adenocarcinoma of lung; pancreatic neoplasms | Safety, tolerability, and feasibility of recombinant anti-mesothelin immunotoxin in combination with immune-depleting regimen | NCT01362790 (active, not recruiting) | ||
| Phase 1 | Leukemia, B cell; lymphoma, Hodgkin’s lymphoma; non-Hodgkin’s lymphoma, B cell | Preventing graft rejection | NCT01087294 (recruiting) | ||
| Phase 1 | Chronic lymphocytic leukemia; B cell non-Hodgkin's lymphoma | Synergy between bendamustine and purine analogs in killing cancer cells | NCT01352312 (active, not recruiting) | ||
| Vadadustat (AKB-6548) | Hypoxia-inducible factor-prolyl hydroxylase (PHD) inhibitor | Phase 3 | Anemia; non-dialysis-dependent chronic kidney disease | Correction of anemia and maintenance of hemoglobin | NCT02648347 (recruiting) |
| Phase 3 | Anemia; dialysis-dependent chronic kidney disease | ↓ | NCT02865850 (recruiting) | ||
| Phase 3 | Anemia; non-dialysis-dependent chronic kidney disease | ↓ | NCT02680574 (recruiting) | ||
| Phase 3 | Anemia in subjects With DD-CKD | ↓ | NCT02892149 (recruiting) | ||
| Phase 2 | Anemia; dialysis-dependent chronic kidney disease | ↓ | NCT03054350 (active, not recruiting) | ||
| Phase 2 | Anemia; non-dialysis dependent chronic kidney disease | ↓ | NCT03054337 (active, not recruiting) | ||
| Phase 2 | Anemia; dialysis-dependent chronic kidney disease | ↓ | NCT03140722 (recruiting) | ||
| Daprodustat (GSK1278863) | PHD inhibitor | Phase 3 | Anemia | Maintain hemoglobin | NCT03029208 (recruiting) |
| Phase 3 | Anemia | ↓ | NCT02969655 (recruiting) | ||
| Phase 3 | Anemia | ↓ | NCT02876835 (recruiting) | ||
| Phase 3 | Anemia | ↓ | NCT02879305 (recruiting) | ||
| Phase 2 | Anemia | ↓ | NCT03029247 (not yet recruiting) | ||
| Roxadustat (FG-4592); also known as AP1517 | PHD inhibitor | Phase 3 | Anemia in chronic kidney disease in nondialysis patients | To treat anemia | NCT02021318 (recruiting) |
| Phase 3 | Anemia | ↓ | NCT02174627 (active, not recruiting) | ||
| Phase 3 | Anemia; end-stage renal disease (ESRD) | ↓ | NCT02278341 (active, not recruiting) | ||
| Phase 3 | Anemia | ↓ | NCT02174731 (recruiting) | ||
| Roxadustat (FG-4592); also known as AP1517 | PHD inhibitor | Phase 3 | Anemia in chronic kidney disease in nondialysis patients | To treat anemia | NCT01887600 (active, not recruiting) |
| Phase 3 | CKD anemia in stable dialysis patients | ↓ | NCT02273726 (recruiting) | ||
| Phase 3 | Anemia in incident dialysis patients | ↓ | NCT02052310 (recruiting) | ||
| Phase 1 | Normal renal function; impaired renal function | Evaluate pharmacokinetics in subjects with different degrees of renal function | NCT02965040 (recruiting) | ||
| ASP1517 | PHD inhibitor | Phase 3 | Chronic kidney disease | Oral dosing; treatment of anemia | NCT02988973 (recruiting) |
| Phase 3 | Peritoneal dialysis chronic kidney disease patients with anemia | ↓ | NCT02780726 (active, not recruiting) | ||
| Phase 3 | Chronic kidney disease | ↓ | NCT02964936 (recruiting) | ||
| Phase 3 | Hemodialysis chronic kidney disease patients With anemia | ↓ | NCT02952092 (recruiting) | ||
| Remote Ischemic Preconditioning | N/A | Myocardial infarction | Effective endogenous cardiac protection, assess major adverse cardiovascular events such as cardiovascular death, spontaneous myocardial infarction, unplanned revascularization and stroke | NCT02843464 (not yet recruiting) | |
| N/A | Myocardial infarction, acute | Effective endogenous cardiac protection | NCT03018873 (not yet recruiting) |
↓, Same as previous indication.