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Istradefylline

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Also known as IstradefilinaKW-6002NourianzNouriastSID170466116

Summary

Istradefylline (CHEMBL431770) is an approved small molecule (ATC N04CX01) targeting ADORA1, ADORA2A, and ADORA2B; indicated across 4 conditions including parkinson disease and liver disorder.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: N04CX01
  • Targets: 4 (ADORA1, ADORA2A, ADORA2B…)
  • Indications: 4 conditions
  • Clinical trials: 24
  • Chemistry: 384.4 Da · C20H24N4O4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL431770
NameIstradefylline
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID5311037
ATCN04CX01
Molecular formulaC20H24N4O4
Molecular weight384.4
InChIKeyIQVRBWUUXZMOPW-PKNBQFBNSA-N

SMILES: CCN1C2=C(C(=O)N(C1=O)CC)N(C(=N2)/C=C/C3=CC(=C(C=C3)OC)OC)C

IUPAC name: 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione

Also known as: Istradefilina, Istradefylline, KW-6002, Nourianz, Nouriast, istradefylline, ISTRADEFYLLINE, SID170466116

Patent coverage: 683 distinct patent families (1,769 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,685 (95%) 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).

GeneTargetActionpAffinityCancer dependencyUniProt
ADORA1A1 receptorAntagonist6.080.3%P30542
ADORA2AA2A receptorAntagonist7.920.4%P29274
ADORA2BA2B receptorAntagonist50.5%P29275
ADORA3A3 receptorAntagonist5.350%P0DMS8

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Amine oxidase [flavin-containing] B, 5-hydroxytryptamine receptor 1A, Adenosine receptor A1, Adenosine receptor A2a, 3’,5’-cyclic-AMP phosphodiesterase 4A, Adenosine receptor A2b, Adenosine receptor A3, 3’,5’-cyclic-AMP phosphodiesterase 4D, Adenosine receptor A2a, Adenosine receptor A1.

Bioactivity

ChEMBL activities: 67 potent at pChembl ≥ 5 of 71 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
P305438.7Ki2nMCHEMBL_ACT_2067974
P305438.66Ki2.2nMCHEMBL_ACT_13298552
P305438.66Ki2.2nMCHEMBL_ACT_15725515
ADORA2A8.66Ki2.2nMCHEMBL_ACT_1611097
P305438.66Ki2.2nMCHEMBL_ACT_422862
P305438.36Ki4.4nMCHEMBL_ACT_19487838
P305438.35Ki4.46nMCHEMBL_ACT_13848916
P305438.35Ki4.46nMCHEMBL_ACT_2372170
P305438.3Ki5.01nMCHEMBL_ACT_1987445
P305438.29Ki5.15nMCHEMBL_ACT_12045880
P305438.29Ki5.15nMCHEMBL_ACT_2032161
ADORA2A8.22Ki6nMCHEMBL_ACT_2067981
ADORA2A7.92Ki12nMCHEMBL_ACT_13300512
ADORA2A7.92Ki12nMCHEMBL_ACT_13848917
ADORA2A7.92Ki12nMCHEMBL_ACT_14645598
ADORA2A7.92Ki12nMCHEMBL_ACT_18694861
ADORA2A7.92Ki12nMCHEMBL_ACT_18725598
ADORA2A7.92Ki12nMCHEMBL_ACT_24710026
ADORA2A7.92Ki12nMCHEMBL_ACT_24772316
P305437.89Ki13nMCHEMBL_ACT_422861
MAOB7.57Ki27nMCHEMBL_ACT_19480633
ADORA2A7.44Ki36nMCHEMBL_ACT_13298556
ADORA2A7.44Ki36nMCHEMBL_ACT_22756949
ADORA2A7.44Ki36nMCHEMBL_ACT_2677384
ADORA2A7.32Ki47.4nMCHEMBL_ACT_12629440
ADORA2A7.14Ki72nMCHEMBL_ACT_15166816
ADORA2A7.14Ki72nMCHEMBL_ACT_3424226
ADORA2A7.14Ki72nMCHEMBL_ACT_5207175
ADORA2A7.04Ki90.8nMCHEMBL_ACT_12046005
ADORA2A7.04Ki91.2nMCHEMBL_ACT_13299675

Target pathways

Aggregated over 4 target gene(s): ADORA1, ADORA2A, ADORA2B, ADORA3.

Top Reactome pathways

23 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction4ADORA1, ADORA2A, ADORA2B, ADORA3
Signaling by GPCR4ADORA1, ADORA2A, ADORA2B, ADORA3
Class A/1 (Rhodopsin-like receptors)4ADORA1, ADORA2A, ADORA2B, ADORA3
GPCR downstream signalling4ADORA1, ADORA2A, ADORA2B, ADORA3
Adenosine P1 receptors4ADORA1, ADORA2A, ADORA2B, ADORA3
Nucleotide-like (purinergic) receptors4ADORA1, ADORA2A, ADORA2B, ADORA3
GPCR ligand binding4ADORA1, ADORA2A, ADORA2B, ADORA3
Metabolism of proteins2ADORA2A, ADORA2B
G alpha (s) signalling events2ADORA2A, ADORA2B
G alpha (i) signalling events2ADORA1, ADORA3
Surfactant metabolism2ADORA2A, ADORA2B
Disease1ADORA2B
Signaling by NTRKs1ADORA2A
Activation of TRKA receptors1ADORA2A
NGF-independant TRKA activation1ADORA2A
Signaling by NTRK1 (TRKA)1ADORA2A
Infectious disease1ADORA2B
Signaling by Receptor Tyrosine Kinases1ADORA2A
Leishmania infection1ADORA2B
ADORA2B mediated anti-inflammatory cytokines production1ADORA2B
Anti-inflammatory response favouring Leishmania parasite infection1ADORA2B
Leishmania parasite growth and survival1ADORA2B
Parasitic Infection Pathways1ADORA2B

Dominant GO biological processes

GO termTargets
signal transduction4
G protein-coupled receptor signaling pathway4
G protein-coupled adenosine receptor signaling pathway4
inflammatory response3
negative regulation of cell population proliferation3
vasodilation3
presynaptic modulation of chemical synaptic transmission3
phagocytosis2
cell-cell signaling2
response to purine-containing compound2
excitatory postsynaptic potential2
apoptotic signaling pathway2
negative regulation of inflammatory response2
adenylate cyclase-activating G protein-coupled receptor signaling pathway2
regulation of norepinephrine secretion2

Indications & clinical

Indications

4 indications (1 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
Parkinson disease4MONDO:0005180MONDO:0005180
liver disorder1MONDO:0005154EFO:0001421
drug dependence1MONDO:0005303EFO:0003890
amyotrophic lateral sclerosis1MONDO:0004976MONDO:0004976

Clinical trials

Total trials: 24.

Phase distribution

PhaseTrials
PHASE29
PHASE38
PHASE13
PHASE41
PHASE2/PHASE31
PHASE1/PHASE21
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05885360PHASE4COMPLETEDIstradefylline Effect Protocol on Parkinson’s Disease Tremor
NCT00199381PHASE3TERMINATEDAn Extension of Istradefylline in North American Parkinson’s Disease Patients Who Have Completed Study 6002-INT-001
NCT00199394PHASE3COMPLETEDA Study of Istradefylline (KW-6002) for the Treatment of Parkinson’s Disease
NCT00199407PHASE3COMPLETEDA Study of Istradefylline (KW-6002) for the Treatment of Parkinson’s Disease in Patients Taking Levodopa
NCT00199420PHASE3COMPLETEDA Study of Istradefylline (KW-6002) in Treating Patients With Parkinson’s Disease on Levodopa
NCT00203957PHASE3COMPLETEDStudy of KW-6002 (Istradefylline) in Parkinson’s Disease in Patients With Motor Response Complications on Levodopa
NCT00955045PHASE2/PHASE3COMPLETEDA Long-Term, Safety Study With a Flexible Dose Range of KW-6002 in Patients With Motor Response Complications on Levodopa/Carbidopa Therapy
NCT00955526PHASE3COMPLETEDStudy of KW-6002 (Istradefylline) for the Treatment of Parkinson’s Disease in Patients Taking Levodopa
NCT00957203PHASE3COMPLETEDLong-Term Safety Study of KW-6002 (Istradefylline) in Parkinson’s Disease Patients
NCT01968031PHASE3COMPLETEDA 12-week Randomized Study to Evaluate Oral Istradefylline in Subjects With Moderate to Severe Parkinson’s Disease
NCT05217498PHASE1/PHASE2NOT_YET_RECRUITINGCombining Low Oxygen Therapy and an Adenosine A2a Receptor Antagonist to Improve Functional Mobility After Spinal Cord Injury
NCT00006337PHASE2COMPLETEDKW-6002 to Treat Parkinson’s Disease
NCT00199355PHASE2COMPLETEDA Study of Istradefylline (KW-6002) for the Treatment of Parkinson’s Disease in Patients Taking Levodopa
NCT00199433PHASE2COMPLETEDA Study of Istradefylline (KW-6002) as Monotherapy in Parkinson’s Disease (PD) Patients
NCT00199446PHASE2COMPLETEDStudy of Istradefylline (KW-6002) for the Treatment of Restless Legs Syndrome
NCT00250393PHASE2COMPLETEDA Study of Istradefylline (KW-6002) for the Treatment of Parkinson’s Disease
NCT00455507PHASE2COMPLETEDA Phase 2b Study of Istradefylline (KW-6002) for the Treatment of Parkinson’s Disease in Patients Taking Levodopa
NCT00456586PHASE2COMPLETED12-Week, Double-Blind, Placebo-Controlled, Randomized Study of the Efficacy of 40 mg/Day KW-6002 in Parkinson’s Disease Patients on Levodopa/Carbidopa
NCT00456794PHASE2COMPLETED12-Week, Double-Blind, Placebo-Controlled Study of 20 and 60 mg/Day Istradefylline in Parkinson’s Disease Patients on Levodopa/Carbodopa
NCT05333549PHASE2COMPLETEDIstradefylline for Parkinson Disease With Cognitive Impairment
NCT02174250PHASE1COMPLETEDThe Effect of Rifampin on the Metabolism of Istradefylline in Healthy Volunteers.
NCT02256033PHASE1COMPLETEDEffect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline
NCT02609477PHASE1COMPLETEDA Study to Evaluate Abuse Potential of Istradefylline
NCT05182151Not specifiedTERMINATEDEffect of Istradefylline Treatment on Behavioral Measures of Apathy in Parkinson’s Disease.

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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:

MoleculeSourceStatusShared targets
ADENOSINEChEMBLPhase 4 (approved)ADORA1, ADORA2A, ADORA2B, ADORA3
CAFFEINEChEMBLPhase 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
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
ERLOTINIBChEMBLPhase 4 (approved)ADORA2A, 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