istradefylline 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
N-methylated xanthine derivatives 4882 155270-99-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nourianz
  • istradefylline
  • nouriast
  • KW-6002
  • KW6002
selective antagonist at the A2A receptor, used in the treatment of Parkinson's disease
  • Molecular weight: 384.44
  • Formula: C20H24N4O4
  • CLOGP: 3.03
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 0
  • TPSA: 76.90
  • ALOGS: -3.33
  • ROTB: 6
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 68 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.061 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.583 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 80.910 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 10.257 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 9.170 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 24.360 % High 1
herg hERG pIC50 4.493 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 6.095 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 28.973 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 4.640 % High 1
kinase-safety-class ACVR2A,ACVR2B,ALK,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,ERBB2,FLT3,GRK2,ITK,JAK1,MAP3K21,MAPK7,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKDC,SIK2,SIK3,STK33,TEK,TTK 37
kinase-selectivity-class ACVR2A,ACVR2B,AXL,BRAF,CAMK2D,CDK16,CDK9,CSF1R,DDR1,FLT3,GRK2,IRAK1,IRAK3,MAP2K3,MAP2K6,MAP3K21,MAPK12,MAPK7,MARK4,MET,MTOR,PDK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKDC,SIK2,SIK3,STK33,TEK,ULK1,ZAP70 33
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.443 High 1
mh-clint Mouse hepatocyte intrinsic clearance 16.749 High 1
mppb Mouse plasma protein binding (% unbound) 4.250 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.216 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 9.020 % High 1
rh-clint Rat hepatocyte intrinsic clearance 4.710 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 54.540 % High 1
rppb Rat plasma protein binding (% unbound) 2.730 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 12.078 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 27, 2019 FDA KYOWA KIRIN
March 15, 2013 PMDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Dyskinesia 119.42 50.05 28 347 36506 90591566
Hallucination 62.37 50.05 19 356 65940 90562132

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hallucination 50.66 41.30 19 360 57488 42563468
Dyskinesia 48.46 41.30 15 364 25375 42595581

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Dyskinesia 147.56 47.21 40 778 51406 110537075
Hallucination 93.26 47.21 33 785 101399 110487082
Hallucination, visual 69.28 47.21 21 797 39584 110548897
Death 65.28 47.21 48 770 698821 109889660

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N04CX01 NERVOUS SYSTEM
ANTI-PARKINSON DRUGS
OTHER ANTIPARKINSON DRUGS
Other antiparkinson drugs
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D058914 Purinergic Antagonists
MeSH PA D058915 Purinergic P1 Receptor Antagonists
MeSH PA D058917 Adenosine A2 Receptor Antagonists
CHEBI has role CHEBI:48407 antiparkinson drug

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Parkinson's disease indication 49049000 DOID:14330




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 1.59 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
20MG NOURIANZ KYOWA KIRIN N022075 Aug. 27, 2019 RX TABLET ORAL 7727993 Jan. 28, 2028 A METHOD OF REDUCING OFF TIME FROM L-DOPA THERAPY, COMPRISING ADMINISTERING, TO A HUMAN PATIENT WITH PARKINSONS DISEASE, AN EFFECTIVE AMOUNT OF ISTRADEFYLLINE, WHEREIN THE PATIENT CURRENTLY RECEIVES SAID L-DOPA THERAPY
40MG NOURIANZ KYOWA KIRIN N022075 Aug. 27, 2019 RX TABLET ORAL 7727993 Jan. 28, 2028 A METHOD OF REDUCING OFF TIME FROM L-DOPA THERAPY, COMPRISING ADMINISTERING, TO A HUMAN PATIENT WITH PARKINSONS DISEASE, AN EFFECTIVE AMOUNT OF ISTRADEFYLLINE, WHEREIN THE PATIENT CURRENTLY RECEIVES SAID L-DOPA THERAPY

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Adenosine receptor A2a GPCR ANTAGONIST Ki 8.66 CHEMBL SCIENTIFIC LITERATURE
Amine oxidase [flavin-containing] B Enzyme Ki 7.57 CHEMBL
Adenosine receptor A1 GPCR Ki 6.08 CHEMBL
Adenosine receptor A3 GPCR Ki 5.35 CHEMBL
Adenosine receptor A2b GPCR Ki 5.75 CHEMBL
Adenosine receptor A1 GPCR Ki 6.82 CHEMBL
Adenosine receptor A2a GPCR Ki 8.70 CHEMBL

External reference:

IDSource
2GZ0LIK7T4 UNII
D04641 KEGG_DRUG
4038742 VANDF
C0673470 UMLSCUI
CHEBI:134726 CHEBI
JQ9 PDB_CHEM_ID
CHEMBL431770 ChEMBL_ID
5311037 PUBCHEM_CID
DB11757 DRUGBANK_ID
8387 INN_ID
C111599 MESH_SUPPLEMENTAL_RECORD_UI
5608 IUPHAR_LIGAND_ID
2199015 RXNORM
322306 MMSL
37365 MMSL
d09365 MMSL
018108 NDDF
789546007 SNOMEDCT_US
789550000 SNOMEDCT_US
2GZ0LIK7T4 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
NOURIANZ HUMAN PRESCRIPTION DRUG LABEL 1 42747-602 TABLET, FILM COATED 20 mg ORAL NDA 31 sections
NOURIANZ HUMAN PRESCRIPTION DRUG LABEL 1 42747-604 TABLET, FILM COATED 40 mg ORAL NDA 31 sections