Theophylline Anhydrous
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Also known as Theophylline
Summary
Theophylline Anhydrous (CHEMBL190) is an approved protein vasodilator agent targeting ADORA1, ADORA2A, and ADORA2B.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Protein
- Targets: 4 (ADORA1, ADORA2A, ADORA2B…)
- Clinical trials: 53
- Chemistry: 180.16 Da · C7H8N4O2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL190 |
| Name | Theophylline Anhydrous |
| Type | Protein |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 2153 |
| ChEBI | CHEBI:28177 |
| Molecular formula | C7H8N4O2 |
| Molecular weight | 180.16 |
| InChIKey | ZFXYFBGIUFBOJW-UHFFFAOYSA-N |
SMILES: CN1C2=C(C(=O)N(C1=O)C)NC=N2
IUPAC name: 1,3-dimethyl-7H-purine-2,6-dione
ChEBI definition: A dimethylxanthine having the two methyl groups located at positions 1 and 3. It is structurally similar to caffeine and is found in green and black tea.
Pharmacological roles (ChEBI): vasodilator agent, bronchodilator agent, muscle relaxant, EC 3.1.4.* (phosphoric diester hydrolase) inhibitor, anti-asthmatic drug, anti-inflammatory agent, immunomodulator, adenosine receptor antagonist.
Other ChEBI roles (chemical / environmental): drug metabolite, fungal metabolite, human blood serum metabolite.
Also known as: Theophylline
Parent form; salt/anhydrous children: CHEMBL1200434, CHEMBL1355736, CHEMBL1370561, CHEMBL2104089, CHEMBL2107084
Patent coverage: 72,055 distinct patent families (168,475 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 168,418 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| ADORA1 | A1 receptor | Antagonist | 5.2 | 0.3% | P30542 |
| ADORA2A | A2A receptor | Antagonist | 5.8 | 0.4% | P29274 |
| ADORA2B | A2B receptor | Antagonist | 5.04 | 0.5% | P29275 |
| ADORA3 | A3 receptor | Antagonist | 4.65 | 0% | P0DMS8 |
Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: ATPase family AAA domain-containing protein 2.
Bioactivity
No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).
Target pathways
Aggregated over 4 target gene(s): ADORA1, ADORA2A, ADORA2B, ADORA3.
Top Reactome pathways
23 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Signal Transduction | 4 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| Signaling by GPCR | 4 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| Class A/1 (Rhodopsin-like receptors) | 4 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| GPCR downstream signalling | 4 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| Adenosine P1 receptors | 4 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| Nucleotide-like (purinergic) receptors | 4 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| GPCR ligand binding | 4 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| Metabolism of proteins | 2 | ADORA2A, ADORA2B |
| G alpha (s) signalling events | 2 | ADORA2A, ADORA2B |
| G alpha (i) signalling events | 2 | ADORA1, ADORA3 |
| Surfactant metabolism | 2 | ADORA2A, ADORA2B |
| Disease | 1 | ADORA2B |
| Signaling by NTRKs | 1 | ADORA2A |
| Activation of TRKA receptors | 1 | ADORA2A |
| NGF-independant TRKA activation | 1 | ADORA2A |
| Signaling by NTRK1 (TRKA) | 1 | ADORA2A |
| Infectious disease | 1 | ADORA2B |
| Signaling by Receptor Tyrosine Kinases | 1 | ADORA2A |
| Leishmania infection | 1 | ADORA2B |
| ADORA2B mediated anti-inflammatory cytokines production | 1 | ADORA2B |
| Anti-inflammatory response favouring Leishmania parasite infection | 1 | ADORA2B |
| Leishmania parasite growth and survival | 1 | ADORA2B |
| Parasitic Infection Pathways | 1 | ADORA2B |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| signal transduction | 4 |
| G protein-coupled receptor signaling pathway | 4 |
| G protein-coupled adenosine receptor signaling pathway | 4 |
| inflammatory response | 3 |
| negative regulation of cell population proliferation | 3 |
| vasodilation | 3 |
| presynaptic modulation of chemical synaptic transmission | 3 |
| phagocytosis | 2 |
| cell-cell signaling | 2 |
| response to purine-containing compound | 2 |
| excitatory postsynaptic potential | 2 |
| apoptotic signaling pathway | 2 |
| negative regulation of inflammatory response | 2 |
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | 2 |
| regulation of norepinephrine secretion | 2 |
Indications & clinical
Indications
0 indications (0 at ChEMBL trial phase 4).
Clinical trials
Total trials: 53.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 11 |
| PHASE2 | 11 |
| Not specified | 10 |
| PHASE1 | 9 |
| PHASE3 | 6 |
| PHASE2/PHASE3 | 5 |
| EARLY_PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT03718403 | PHASE4 | RECRUITING | Effect of Theophylline in Pseudohypoparathyroidism |
| NCT00492518 | PHASE4 | COMPLETED | Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy |
| NCT00756418 | PHASE4 | COMPLETED | Montelukast Post-marketing Comparative Study With Theophyline Added to Inhaled Corticosteroid (0476-396) |
| NCT01010178 | PHASE4 | COMPLETED | Can Airflow Limitation in Chronic Obstructive Pulmonary Disease (COPD) be Reversible by Drugs? |
| NCT01601132 | PHASE4 | COMPLETED | Drug Interaction Study of Colchicine and Theophylline |
| NCT01684683 | PHASE4 | COMPLETED | The Effect of Theophylline in the Treatment of Bronchiectasis |
| NCT01696214 | PHASE4 | COMPLETED | A Pilot Study to Determine the Feasibility and Utility of Implementing of the Full Scale TOM Trial |
| NCT01769898 | PHASE4 | COMPLETED | The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis |
| NCT02261727 | PHASE4 | COMPLETED | Theophylline and Steroids in Chronic Obstructive Pulmonary Disease (COPD) Study |
| NCT02537691 | PHASE4 | COMPLETED | Longitudinal Cohort Study in Participants With Severe Asthma to Assess Biomarkers |
| NCT07171021 | PHASE4 | COMPLETED | The Effect of Oral Theophylline on Traumatic Anosmia |
| NCT00000578 | PHASE3 | COMPLETED | NHLBI/NICHD Collaborative Studies of Asthma in Pregnancy |
| NCT00003684 | PHASE3 | COMPLETED | Theophylline in Treating Cancer Patients With Shortness of Breath |
| NCT00119496 | PHASE2/PHASE3 | COMPLETED | Rosiglitazone Versus Theophylline in Asthmatic Smokers |
| NCT00252785 | PHASE3 | COMPLETED | Efficacy & Safety of Symbicort® TURBUHALER® 160/4.5 µg Twice Daily & Pulmicort® TURBUHALER® 200 µg Twice Daily + Theolong® Tablet 200 mg Twice Daily in Japanese Asthmatic Patients |
| NCT00252863 | PHASE3 | COMPLETED | DESOLO - SiT Peri-Launch: A Comparison of Symbicort Single Inhaler Therapy and Conventional Best Practice for the Treatment of Persistent Asthma in Adults |
| NCT00299858 | PHASE2/PHASE3 | COMPLETED | Theophylline in Chronic Obstructive Pulmonary Disease |
| NCT01066728 | PHASE2/PHASE3 | COMPLETED | CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity |
| NCT01599871 | PHASE3 | COMPLETED | Low-dose Theophylline as Anti-inflammatory Enhancer in Severe Chronic Obstructive Pulmonary Disease |
| NCT01902758 | PHASE2/PHASE3 | COMPLETED | Drug Combination on Exercise Performance at High Altitude |
| NCT02088502 | PHASE2/PHASE3 | UNKNOWN | Theophylline, N-acetylcysteine, and Theophylline Plus N-acetylcysteine in Preventing Contrast-induced Nephropathy |
| NCT02340520 | PHASE3 | COMPLETED | Enhancement of Corticosteroid Efficacy in COPD |
| NCT03029429 | PHASE2 | ACTIVE_NOT_RECRUITING | Theophylline Treatment for Pseudohypoparathyroidism |
| NCT04551170 | PHASE2 | ACTIVE_NOT_RECRUITING | Theophylline Treatment for Pseudohypoparathyroidism - Children 2-12 Years Old |
| NCT05076682 | PHASE2 | RECRUITING | Reverse Triple Negative Immune Resistant Breast Cancer |
| NCT00003808 | PHASE2 | COMPLETED | Theophylline in Treating Patients With In Situ, Stage I, or Stage II Chronic Lymphocytic Leukemia |
| NCT00241631 | PHASE2 | COMPLETED | Enhancement of in-Vitro GC Function in Patients With COPD |
| NCT02463409 | PHASE2 | COMPLETED | Theophylline as a Treatment for Children With Pseudohypoparathyroidism Type 1a (Albright Hereditary Osteodystrophy) |
| NCT02479451 | PHASE2 | COMPLETED | Helping Olfaction and Nutrition On Renal Replacement |
| NCT03990766 | PHASE2 | COMPLETED | Smell Changes & Efficacy of Nasal Theophylline |
| NCT04789499 | PHASE2 | COMPLETED | Smell in Covid-19 and Efficacy of Nasal Theophylline |
| NCT05717049 | PHASE2 | COMPLETED | Theophylline Effects in the Fontan Circulation |
| NCT05947643 | PHASE2 | COMPLETED | Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3) |
| NCT00779259 | PHASE1 | COMPLETED | Drug - Drug Interaction Study Between Quinine Sulfate and Theophylline |
| NCT00983905 | PHASE1 | COMPLETED | Drug-Drug Interaction Study of Colchicine and Theophylline |
| NCT01017939 | PHASE1 | COMPLETED | A Drug-Drug Interaction Study of Abiraterone Acetate Plus Prednisone With Dextromethorphan and Theophylline in Patients With Metastatic Castration-Resistant Prostate Cancer |
| NCT01263106 | PHASE1 | COMPLETED | A Study of LY2216684 and Theophylline in Healthy Subjects |
| NCT01566565 | PHASE1 | COMPLETED | The Safety Evaluation of Drug Combinations Against High Altitude Pulmonary Hypertension |
| NCT01799161 | PHASE1 | WITHDRAWN | Combination of gp96-Ig Vaccine, Theophylline and Oxygen for the Treatment of Patients With Advanced, Relapsed or Metastatic Non-Small Cell Lung Cancer |
| NCT02080078 | PHASE1 | TERMINATED | A Phase I Dose Escalation Study of Erlotinib in Combination With Theophylline |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 6 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
476 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ADENOSINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| CAFFEINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| ISTRADEFYLLINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| REGADENOSON | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| BINODENOSON | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| ROLOFYLLINE | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| TONAPOFYLLINE | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| TOZADENANT | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| TRABODENOSON | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| CIFORADENANT | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| DERENOFYLLINE | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| ENPROFYLLINE | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| IMARADENANT | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| TECADENOSON | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| VIPADENANT | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B, ADORA3 |
| Fidaxomicin | ChEMBL + PubChem | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| Linagliptin | ChEMBL + PubChem | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| Pyrazinamide | ChEMBL + PubChem | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| CLOFARABINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| ECONAZOLE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| EPALRESTAT | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| FEDRATINIB | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| MEFLOQUINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| MICONAZOLE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| NEVIRAPINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| NIFEDIPINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| NIMESULIDE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| NISOLDIPINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| NITAZOXANIDE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| PENTOSTATIN | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| PYRVINIUM | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| RIFAMPIN | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| RIFAXIMIN | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| SUNITINIB | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| TAMOXIFEN | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A, ADORA3 |
| APADENOSON | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA3 |
| DIACEREIN | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA3 |
| NAMODENOSON | ChEMBL | Phase 3 | ADORA1, ADORA2A, ADORA3 |
| ETRUMADENANT | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B |
| METRIFUDIL | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA3 |
| SONEDENOSON | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA2B |
| TOFIMILAST | ChEMBL | Phase 2 | ADORA1, ADORA2A, ADORA3 |
| Afatinib | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| Apixaban | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| Binimetinib | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| Bosentan | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| chenodiol | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| Dihydroergotamine | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| Fulvestrant | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| Imipenem | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| Propoxyphene | PubChem | Approved | ADORA1, ADORA2A, ADORA3 |
| ALPIDEM | ChEMBL | Phase 4 (approved) | ADORA1, ADORA3 |
| AMPHETAMINE | ChEMBL | Phase 4 (approved) | ADORA1, ADORA2A |
| BALSALAZIDE | ChEMBL | Phase 4 (approved) | ADORA2A, ADORA3 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | ADORA2A, ADORA3 |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | ADORA2A, ADORA3 |
| ENASIDENIB | ChEMBL | Phase 4 (approved) | ADORA1, ADORA3 |
| ERLOTINIB | ChEMBL | Phase 4 (approved) | ADORA2A, ADORA3 |
Related Atlas pages
- Genes: ADORA1, ADORA2A, ADORA2B, ADORA3
- Drugs: Adenosine, Caffeine, Istradefylline, Regadenoson, Binodenoson, Rolofylline, Tonapofylline, Tozadenant, Trabodenoson, Fidaxomicin, Linagliptin, Pyrazinamide, Clofarabine, Clotrimazole, Diethylstilbestrol, Econazole, Epalrestat, Fedratinib, Mefloquine, Miconazole, Nevirapine, Nifedipine, Nimesulide, Nisoldipine, Nitazoxanide, Pentostatin, Pyrvinium, Rifampin, Rifaximin, Sunitinib, Tamoxifen, Apadenoson, Diacerein, Namodenoson, Afatinib, Apixaban, Binimetinib, Bosentan, chenodiol, Dihydroergotamine, Fulvestrant, Imipenem, Propoxyphene, Alpidem, Amphetamine, Balsalazide, Bithionol, Daunorubicin, Enasidenib, Erlotinib