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Atlas / Drug / Caffeine

Caffeine

drug
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Also known as Anhydrous caffeineCaffeine anhydrousCaffeine component of anoquanCaffeine component of cafergotCaffeine component of darvon compoundCaffeine component of dhc plusCaffeine component of esgicCaffeine component of excedrinCaffeine component of femcetCaffeine component of fioricetCaffeine component of fiorinalCaffeine component of invagesicCaffeine component of invagesic forteCaffeine component of lanorinalCaffeine component of medigesic plusCaffeine component of migergotCaffeine component of norgesicCaffeine component of orphengesicCaffeine component of orphengesic forte

Summary

Caffeine (CHEMBL113) is an approved small-molecule central nervous system stimulant (ATC N06BC01) targeting ADORA1, ADORA2A, and ADORA2B; indicated across 55 conditions including attention deficit-hyperactivity disorder and migraine disorder.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: N06BC01 (+1 more)
  • Targets: 8 (ADORA1, ADORA2A, ADORA2B…)
  • Indications: 55 conditions
  • Clinical trials: 318
  • Chemistry: 194.19 Da · C8H10N4O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL113
NameCaffeine
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID2519
ChEBICHEBI:27732
ATCN06BC01, D11AX26
Molecular formulaC8H10N4O2
Molecular weight194.19
InChIKeyRYYVLZVUVIJVGH-UHFFFAOYSA-N

SMILES: CN1C=NC2=C1C(=O)N(C(=O)N2C)C

IUPAC name: 1,3,7-trimethylpurine-2,6-dione

ChEBI definition: A trimethylxanthine in which the three methyl groups are located at positions 1, 3, and 7. A purine alkaloid that occurs naturally in tea and coffee.

Pharmacological roles (ChEBI): mutagen, central nervous system stimulant, EC 3.1.4.* (phosphoric diester hydrolase) inhibitor, adenosine receptor antagonist, EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor, ryanodine receptor agonist, adenosine A2A receptor antagonist, psychotropic drug, diuretic, adjuvant, geroprotector.

Other ChEBI roles (chemical / environmental): fungal metabolite, food additive, plant metabolite, environmental contaminant, xenobiotic, human blood serum metabolite, mouse metabolite.

Also known as: Anhydrous caffeine, Caffeine, Caffeine anhydrous, Caffeine component of anoquan, Caffeine component of cafergot, Caffeine component of darvon compound, Caffeine component of dhc plus, Caffeine component of esgic, Caffeine component of excedrin, Caffeine component of femcet, Caffeine component of fioricet, Caffeine component of fiorinal

Parent form; salt/anhydrous children: CHEMBL1200569

Patent coverage: 74,362 distinct patent families (200,591 SureChEMBL compound mentions), from 1 matched compound structure(s). 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).

GeneTargetActionpAffinityCancer dependencyUniProt
ADORA1A1 receptorAntagonist4.970.3%P30542
ADORA2AA2A receptorAntagonist5.60.4%P29274
ADORA2BA2B receptorAntagonist4.980.5%P29275
ADORA3A3 receptorAntagonist4.880%P0DMS8
ITPR1IP3R1Antagonist1.4%Q14643
RYR1RyR11%P21817
RYR2RyR20.3%Q92736
RYR3RyR30%Q15413

Broader ChEMBL bioactivity targets: 32 (assay-derived). Sample: Transient receptor potential cation channel subfamily A member 1, Nuclear receptor ROR-gamma, 4’-phosphopantetheinyl transferase ffp, Nuclear receptor subfamily 2 group E member 1, Adenosine A2 receptor, Adenosine A2 receptor, Phosphodiesterase 1, Adenosine receptor, Cannabinoid receptor 1, Acetylcholinesterase.

Bioactivity

ChEMBL activities: 17 potent at pChembl ≥ 5 of 192 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
CNR19.22AC500.6nMCHEMBL_ACT_25116785
P084827.45Potency35.5nMCHEMBL_ACT_4803580
SIRT36.16Kd690nMCHEMBL_ACT_26164406
P159176Potency1000nMCHEMBL_ACT_4663246
P159175.9Potency1259nMCHEMBL_ACT_4648130
ADORA2A5.61Ki2480nMCHEMBL_ACT_13398787
ADORA2A5.3Ki5012nMCHEMBL_ACT_6284470
ADORA2A5.26Kd5510nMCHEMBL_ACT_24781556
ACHE5.14IC507250nMCHEMBL_ACT_13377217
ACHE5.1IC507943nMCHEMBL_ACT_24973077
NR2E15.1IC507943nMCHEMBL_ACT_24973087
ADORA2A5.07AC508500nMCHEMBL_ACT_25152529
P305435.03Ki9400nMCHEMBL_ACT_2335817
ADORA2A5.02Ki9560nMCHEMBL_ACT_13398776
ADORA2A5.02IC509600nMCHEMBL_ACT_24973065
ADORA2B5Ki10000nMCHEMBL_ACT_19362164
GDA5Ki10000nMCHEMBL_ACT_24973084

Target pathways

Aggregated over 8 target gene(s): ADORA1, ADORA2A, ADORA2B, ADORA3, ITPR1, RYR1, RYR2, RYR3.

Top Reactome pathways

66 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction5ADORA1, ADORA2A, ADORA2B, ADORA3, ITPR1
Signaling by GPCR5ADORA1, ADORA2A, ADORA2B, ADORA3, ITPR1
GPCR downstream signalling5ADORA1, ADORA2A, ADORA2B, ADORA3, ITPR1
Class A/1 (Rhodopsin-like receptors)4ADORA1, ADORA2A, ADORA2B, ADORA3
Muscle contraction4ITPR1, RYR1, RYR2, RYR3
Adenosine P1 receptors4ADORA1, ADORA2A, ADORA2B, ADORA3
Nucleotide-like (purinergic) receptors4ADORA1, ADORA2A, ADORA2B, ADORA3
GPCR ligand binding4ADORA1, ADORA2A, ADORA2B, ADORA3
Cardiac conduction4ITPR1, RYR1, RYR2, RYR3
Ion homeostasis4ITPR1, RYR1, RYR2, RYR3
Stimuli-sensing channels3RYR1, RYR2, RYR3
Transport of small molecules3RYR1, RYR2, RYR3
G alpha (i) signalling events3ADORA1, ADORA3, ITPR1
Ion channel transport3RYR1, RYR2, RYR3
Disease2ADORA2B, ITPR1
Metabolism of proteins2ADORA2A, ADORA2B
G alpha (s) signalling events2ADORA2A, ADORA2B
Infectious disease2ADORA2B, ITPR1
Surfactant metabolism2ADORA2A, ADORA2B
Signaling by Receptor Tyrosine Kinases2ADORA2A, ITPR1
Leishmania infection2ADORA2B, ITPR1
Anti-inflammatory response favouring Leishmania parasite infection2ADORA2B, ITPR1
Leishmania parasite growth and survival2ADORA2B, ITPR1
Parasitic Infection Pathways2ADORA2B, ITPR1
Hemostasis1ITPR1
Opioid Signalling1ITPR1
G-protein mediated events1ITPR1
PLC beta mediated events1ITPR1
Effects of PIP2 hydrolysis1ITPR1
Adaptive Immune System1ITPR1

Dominant GO biological processes

GO termTargets
signal transduction5
response to hypoxia4
G protein-coupled receptor signaling pathway4
G protein-coupled adenosine receptor signaling pathway4
calcium ion transport4
release of sequestered calcium ion into cytosol4
monoatomic ion transport4
calcium-mediated signaling4
monoatomic ion transmembrane transport4
transmembrane transport4
calcium ion transmembrane transport4
inflammatory response3
negative regulation of cell population proliferation3
vasodilation3
response to caffeine3

Indications & clinical

Indications

55 indications (4 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
attention deficit-hyperactivity disorder4MONDO:0007743EFO:0003888
migraine disorder4MONDO:0005277MONDO:0005277
atrial fibrillation3MONDO:0004981EFO:0000275
obesity disorder3MONDO:0011122EFO:0001073
intermittent vascular claudication3MONDO:0005295EFO:0003876
relapsing-remitting multiple sclerosis3MONDO:0005314EFO:0003929
common cold3MONDO:0005709EFO:0007214
coronary artery disorder3MONDO:0005010EFO:0001645
Alzheimer disease3MONDO:0004975MONDO:0004975
Parkinson disease3MONDO:0005180MONDO:0005180
migraine with aura3MONDO:0005475MONDO:0005475
migraine without aura3MONDO:0100431MONDO:0100431
bronchopulmonary dysplasia3MONDO:0019091MONDO:0019091
cocaine dependence2MONDO:0005186EFO:0002610
breast carcinoma2MONDO:0004989EFO:0000305
atopic eczema1MONDO:0004980EFO:0000274
Crohn disease1MONDO:0005011EFO:0000384
neoplasm1MONDO:0005070EFO:0000616
psoriasis1MONDO:0005083EFO:0000676
rheumatoid arthritis1MONDO:0008383EFO:0000685
chronic hepatitis C virus infection1MONDO:0005354EFO:0004220
anemia1MONDO:0002280EFO:0004272
orthostatic hypotension1MONDO:0005469EFO:0005252
infectious disease1MONDO:0005550EFO:0005741
metabolic dysfunction-associated steatohepatitis1MONDO:0007027EFO:1001249
spinal cord injury1MONDO:0043797EFO:1001919
metastatic melanoma1MONDO:0005191EFO:0002617
amblyopia1MONDO:0001020MONDO:0001020
substance-related disorder1MONDO:0002494MONDO:0004938
narcolepsy1MONDO:0021107MONDO:0021107
ulcerative colitis1MONDO:0005101EFO:0000729
HIV infectious disease1MONDO:0005109EFO:0000764
amyotrophic lateral sclerosis1MONDO:0004976MONDO:0004976
type 2 diabetes mellitus1MONDO:0005148MONDO:0005148
alcohol abuse1MONDO:0002046MONDO:0007079
inborn mitochondrial metabolism disorder1MONDO:0004069MONDO:0044970
melanoma1MONDO:0005105EFO:0000756
physiological sexual disorder1MONDO:0002134EFO:0004714
severe acute respiratory syndrome1MONDO:0005091MONDO:0100096
voice disorders0MONDO:0043862EFO:0009692

15 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 318.

Phase distribution

PhaseTrials
Not specified167
PHASE170
PHASE427
PHASE321
PHASE213
EARLY_PHASE110
PHASE2/PHASE35
PHASE1/PHASE25

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06763172PHASE4RECRUITINGEffects of Caffeine on Reinforcement Learning in Healthy Adults Using PET/MRI
NCT07022496PHASE4RECRUITINGAssessment of Oral Caffeine Intake in Changing the Severity of Acute Migraine Attack Using VAS Score Among Patients Attending Headache and Neurology Outpatients Clinic of Ainshams University Hospitals
NCT07212803PHASE4RECRUITINGEffects of Energy Drinks on Cardiovascular Endpoints
NCT00117520PHASE4COMPLETEDThe Effect of Caffeine in Elderly Citizens
NCT00430170PHASE4COMPLETEDDoes Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
NCT00495183PHASE4UNKNOWNEfficacy of Caffeine, With and Without Biperiden, as a Maintenance Treatment for Cocaine Dependence
NCT00781586PHASE4COMPLETEDEfficacy of ONE A DAY Weightsmart Advanced Versus Caffeine and Placebo on Energy Expenditure, Thermogenesis and Perceived Energy Levels in Women.
NCT00851175PHASE4COMPLETEDIs Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?
NCT00981955PHASE4COMPLETEDThe Effects of Caffeine and L-theanine Both Alone and in Combination on Cerebral Blood Flow, Cognition and Mood
NCT01048515PHASE4COMPLETEDThe Effect of Caffeine in Elderly Citizen Following Eight Hour Abstinence From Caffeine Containing Drinks & Foods
NCT01248468PHASE4COMPLETEDEfficacy and Safety of Acetaminophen, Aspirin and Caffeine With Sumatriptan in the Acute Treatment of Migraine
NCT01402089PHASE4COMPLETEDCytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients
NCT01466348PHASE4COMPLETEDEffects of a Common Cold Treatment on Cognitive Function
NCT01693809PHASE4UNKNOWNThe Effects of Caffeine on Vestibular Evoked Myogenic Potentials in Healthy Subjects
NCT01766050PHASE4COMPLETEDStudy to Evaluate Effect of Belatacept on Pharmacokinetics of Inje Cocktail in Healthy Volunteers
NCT01783561PHASE4COMPLETEDEarly Versus Routine Caffeine Administration in Extremely Preterm Neonates
NCT02567968PHASE4COMPLETEDA Study to Determine if Caffeine Accelerates Emergence From Anesthesia
NCT02760615PHASE4WITHDRAWNPhase 4, Vedolizumab-4002 Post-marketing, Disease-Drug-Drug Interaction Study
NCT02825199PHASE4COMPLETEDEffect of Caffeine Intake in Vestibular Function
NCT02974114PHASE4TERMINATEDExploratory Study to Investigate Cognition Function and Mobility in Individuals With Pain
NCT03360903PHASE4COMPLETEDA Study to Determine if Caffeine Accelerates Emergence From Propofol Anesthesia
NCT03400423PHASE4COMPLETEDThe Acute Effects of Caffeine on Exercise and Cognition
NCT03910088PHASE4COMPLETEDPregabalin Versus Hydrocortisone for Postdural Puncture Headache After Spinal for Cesarean
NCT04056650PHASE4TERMINATEDAssessing the Effectiveness of an N-of-1 Platform Using Study of Cognitive Enhancers
NCT04243850PHASE4WITHDRAWNREGROUP: Renohemodynamic Effects empaGliflozin in vaRiOUs Populations
NCT04950660PHASE4COMPLETEDOral Caffeine Use for Pain Management in AIS Patients After Spinal Fusion
NCT05919732PHASE4COMPLETEDAwake Caudal Catheter vs General Anesthesia
NCT04570085PHASE3RECRUITINGEffect of CAFfeine on Cognition in Alzheimer’s Disease
NCT07238465PHASE3RECRUITINGExploring Sympathetic Nervous System Function in Individuals With Down Syndrome
NCT00388128PHASE3COMPLETEDCaffeine and Intermittent Claudication
NCT00495092PHASE2/PHASE3COMPLETEDEfficacy of Caffeine, With and Without Biperiden, in the Detoxification of Cocaine Dependent Patients
NCT00564824PHASE3COMPLETEDThe Impact of Caffeine on Brachial Endothelial Function in Healthy Subjects and in Patients With Ischemic Heart Disease
NCT00826280PHASE3COMPLETEDCaffeine’s Effect on Regadenoson Administration With Single Photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging (MPI)
NCT01426971PHASE3WITHDRAWNIbuprofen Versus Ibuprofen Plus Caffeine in the Treatment of Migraine.
NCT01462318PHASE3COMPLETEDAn Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis
NCT01686646PHASE3COMPLETEDEffects of Two Doses of a Common Cold Treatment on Alertness
NCT01738178PHASE3COMPLETEDCaffeine as a Therapy for Parkinson’s Disease
NCT01842633PHASE3TERMINATEDClinical Study to Evaluate Efficacy of New Paracetamol Formulation Compared to Ibuprofen in Headache
NCT01929031PHASE3COMPLETEDEfficacy and Safety of Ibuprofen and Caffeine in Dental Pain
NCT02048215PHASE3COMPLETEDEffect on Energy Metabolism at Cellular Level of Diet Plus Treatment With Ephedrine and Caffeine in Obesity

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 9 clinical and 120 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

478 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
ADENOSINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA2B, ADORA3
ISTRADEFYLLINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA2B, ADORA3
REGADENOSONChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA2B, ADORA3
THEOPHYLLINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA2B, ADORA3
BINODENOSONChEMBLPhase 3ADORA1, ADORA2A, ADORA2B, ADORA3
ROLOFYLLINEChEMBLPhase 3ADORA1, ADORA2A, ADORA2B, ADORA3
TONAPOFYLLINEChEMBLPhase 3ADORA1, ADORA2A, ADORA2B, ADORA3
TOZADENANTChEMBLPhase 3ADORA1, ADORA2A, ADORA2B, ADORA3
TRABODENOSONChEMBLPhase 3ADORA1, ADORA2A, ADORA2B, ADORA3
CIFORADENANTChEMBLPhase 2ADORA1, ADORA2A, ADORA2B, ADORA3
DERENOFYLLINEChEMBLPhase 2ADORA1, ADORA2A, ADORA2B, ADORA3
ENPROFYLLINEChEMBLPhase 2ADORA1, ADORA2A, ADORA2B, ADORA3
IMARADENANTChEMBLPhase 2ADORA1, ADORA2A, ADORA2B, ADORA3
TECADENOSONChEMBLPhase 2ADORA1, ADORA2A, ADORA2B, ADORA3
VIPADENANTChEMBLPhase 2ADORA1, ADORA2A, ADORA2B, ADORA3
FidaxomicinChEMBL + PubChemPhase 4 (approved)ADORA1, ADORA2A, ADORA3
LinagliptinChEMBL + PubChemPhase 4 (approved)ADORA1, ADORA2A, ADORA3
PyrazinamideChEMBL + PubChemPhase 4 (approved)ADORA1, ADORA2A, ADORA3
CLOFARABINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
CLOTRIMAZOLEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
DIETHYLSTILBESTROLChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
ECONAZOLEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
EPALRESTATChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
FEDRATINIBChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
MEFLOQUINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
MICONAZOLEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
NEVIRAPINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
NIFEDIPINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
NIMESULIDEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
NISOLDIPINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
NITAZOXANIDEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
PENTOSTATINChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
PYRVINIUMChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
RIFAMPINChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
RIFAXIMINChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
SUNITINIBChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
TAMOXIFENChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA3
APADENOSONChEMBLPhase 3ADORA1, ADORA2A, ADORA3
DIACEREINChEMBLPhase 3ADORA1, ADORA2A, ADORA3
NAMODENOSONChEMBLPhase 3ADORA1, ADORA2A, ADORA3
ETRUMADENANTChEMBLPhase 2ADORA1, ADORA2A, ADORA2B
METRIFUDILChEMBLPhase 2ADORA1, ADORA2A, ADORA3
SONEDENOSONChEMBLPhase 2ADORA1, ADORA2A, ADORA2B
TOFIMILASTChEMBLPhase 2ADORA1, ADORA2A, ADORA3
AfatinibPubChemApprovedADORA1, ADORA2A, ADORA3
ApixabanPubChemApprovedADORA1, ADORA2A, ADORA3
BinimetinibPubChemApprovedADORA1, ADORA2A, ADORA3
BosentanPubChemApprovedADORA1, ADORA2A, ADORA3
chenodiolPubChemApprovedADORA1, ADORA2A, ADORA3
DihydroergotaminePubChemApprovedADORA1, ADORA2A, ADORA3
FulvestrantPubChemApprovedADORA1, ADORA2A, ADORA3
ImipenemPubChemApprovedADORA1, ADORA2A, ADORA3
PropoxyphenePubChemApprovedADORA1, ADORA2A, ADORA3
DANTROLENEChEMBL + PubChemPhase 4 (approved)ADORA1, RYR2
ALPIDEMChEMBLPhase 4 (approved)ADORA1, ADORA3
AMPHETAMINEChEMBLPhase 4 (approved)ADORA1, ADORA2A
BALSALAZIDEChEMBLPhase 4 (approved)ADORA2A, ADORA3
BITHIONOLChEMBLPhase 4 (approved)ADORA2A, ADORA3
DAUNORUBICINChEMBLPhase 4 (approved)ADORA2A, ADORA3
ENASIDENIBChEMBLPhase 4 (approved)ADORA1, ADORA3

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot