General Information of Drug (ID: DM20VSK)

Drug Name
Istradefylline Drug Info
Synonyms
KW 6002; Istradefylline [USAN:INN]; Istradefylline (JAN/USAN/INN); (E)-8-(3,4-Dimethoxystyryl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione; (E)-8-(3,4-Dimethoxystyryl)-1,3-diethyl-7-methylxanthine; 8-((1E)-2-(3,4-Dimethoxyphenyl)ethenyl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione; 8-(2-(3,4-dimethoxyphenyl)ethenyl)-1,3-diethyl-3,7-dihydro-7-methyl-1H-purine-2,6-dione; 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione
Indication
Disease Entry ICD 11 Status REF
Parkinson disease 8A00.0 Approved [1]
Substance use disorder 6C4Z Phase 1 [2]
Cross-matching ID
PubChem CID
5311037
ChEBI ID
CHEBI:134726
CAS Number
CAS 155270-99-8
TTD Drug ID
DM20VSK
VARIDT Drug ID
DR00611
INTEDE Drug ID
DR0892
ACDINA Drug ID
D01185

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DME
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Caffeine DMKBJWP Allergic rhinitis CA08.0 Approved [4]
Regadenoson DM76VHG Radionuclide imaging N.A. Approved [5]
Tozadenant DMATC14 Parkinson disease 8A00.0 Phase 3 [6]
Binodenoson DMVHF8G Hypertension BA00-BA04 Phase 3 [7]
Apadenoson DMD8QTC Coronary artery disease BA80 Phase 3 [8]
Tonapofylline DMBH316 Acute and chronic heart failure BD1Z Phase 2 [9]
Dexefaroxan DMTY4KN Parkinson disease 8A00.0 Phase 2 [10]
AMP-579 DMJ4GPR Hyperlipidaemia 5C80 Phase 2 [11]
BIIB014 DMH7RJ1 Parkinson disease 8A00.0 Phase 2 [12]
MRE-0094 DMQR23W Diabetic foot ulcer BD54 Phase 2 [13]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [14]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [15]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [16]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [17]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [18]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [19]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [20]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [21]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [15]
Verapamil DMA7PEW Angina pectoris BA40 Approved [22]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [23]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [24]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [25]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [26]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [27]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [28]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [20]
Oxaliplatin DMQNWRD Adenocarcinoma 2D40 Approved [29]
Verapamil DMA7PEW Angina pectoris BA40 Approved [30]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [31]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [32]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [33]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [34]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [18]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [22]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [35]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [36]
Dopamine DMPGUCF Acromegaly 5A60.0 Approved [37]
Nicotine DMWX5CO Lung cancer 2C25.0 Approved [38]
Propranolol DM79NTF Angina pectoris BA40 Approved [39]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [40]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [41]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [42]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [43]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [44]
Sulfasalazine DMICA9H Irritable bowel syndrome DD91.0 Approved [45]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [46]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [47]
Verapamil DMA7PEW Angina pectoris BA40 Approved [48]
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [43]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 2C18 (CYP2C18)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Verapamil DMA7PEW Angina pectoris BA40 Approved [49]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [50]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [51]
Phenytoin DMNOKBV Epilepsy 8A60-8A68 Approved [49]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [52]
Diazepam DM08E9O Alcohol withdrawal Approved [53]
Methadone DMTW6IU Advanced cancer 2A00-2F9Z Approved [54]
Dapsone DM4LT8A Acne vulgaris ED80 Approved [55]
Lidocaine DML4ZOT Anaesthesia 9A78.6 Approved [49]
Phenobarbital DMXZOCG Cluster headache 8A81.0 Approved [56]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [23]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [57]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [57]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [49]
Verapamil DMA7PEW Angina pectoris BA40 Approved [58]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [59]
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [60]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [57]
Mycophenolate mofetil DMPQAGE Hepatosplenic T-cell lymphoma Approved [61]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [51]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 2C9 (CYP2C9)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Progesterone DMUY35B Amenorrhea GA20.0 Approved [62]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [63]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [64]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [49]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [65]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [49]
Verapamil DMA7PEW Angina pectoris BA40 Approved [66]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [67]
Estrone DM5T6US Acne vulgaris ED80 Approved [68]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [69]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 2B6 (CYP2B6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [70]
Verapamil DMA7PEW Angina pectoris BA40 Approved [49]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [71]
Estrone DM5T6US Acne vulgaris ED80 Approved [64]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [72]
Irinotecan DMP6SC2 Adenocarcinoma 2D40 Approved [73]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [74]
Nicotine DMWX5CO Lung cancer 2C25.0 Approved [75]
Phenytoin DMNOKBV Epilepsy 8A60-8A68 Approved [76]
Amitriptyline DMK7F9S Depression 6A70-6A7Z Approved [77]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Adenosine A2a receptor (ADORA2A) TTM2AOE AA2AR_HUMAN Modulator [1]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) Main DME DE4LYSA CP3A4_HUMAN Substrate [3]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [3]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [3]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [3]
Cytochrome P450 3A5 (CYP3A5) Main DME DEIBDNY CP3A5_HUMAN Substrate [3]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [3]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [3]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Substrate [3]

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Effects of rifampin on the pharmacokinetics of a single dose of istradefylline in healthy subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201.
4 Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol. 2014 Aug;13(8):767-76.
7 Coronary circulation responses to binodenoson, a selective adenosine A2A receptor agonist. Am J Cardiol. 2007 Jun 1;99(11):1507-12.
8 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3290).
9 2-Amino-5-benzoyl-4-phenylthiazoles: Development of potent and selective adenosine A1 receptor antagonists. Bioorg Med Chem. 2010 Mar 15;18(6):2195-2203.
10 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
11 Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning. Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2746-53.
12 Novel pharmacological targets for the treatment of Parkinson's disease. Nat Rev Drug Discov. 2006 Oct;5(10):845-54.
13 Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
14 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
15 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
16 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
17 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
18 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
19 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
20 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
21 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
22 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
23 Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
24 Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
25 Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
26 Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
27 PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
28 The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
29 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
30 Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
31 Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
32 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
33 Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
34 CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
35 Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
36 Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
37 Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
38 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
39 Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
40 Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
41 Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
42 Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
43 Drug Interactions Flockhart Table
44 Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
45 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
46 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
47 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
48 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
49 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
50 Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
51 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
52 Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8.
53 Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51. Arch Biochem Biophys. 1997 Feb 15;338(2):157-64.
54 Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol. 1996 Mar;9(2):365-73.
55 CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone. Drug Metab Dispos. 2000 Aug;28(8):865-8.
56 Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos. 2001 Mar;29(3):242-51.
57 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
58 Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
59 Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
60 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
61 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
62 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
63 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
64 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
65 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
66 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
67 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
68 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
69 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
70 Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
71 Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
72 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
73 Drugs that may have potential CYP2B6 interactions.
74 Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
75 Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
76 PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
77 Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.