Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMM74PK)

Drug Name
Atrasentan Drug Info
Synonyms
Xinlay; Atrasentan [INN]; A 127722; A 147627; ABT 627; A-127722; A-147627; ABT-627; Xinlay (TN); A-127722.5; (+)-A 127722; (+)-A-127722; (11C)ABT-627; (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid; 2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(((dibutylamino)carbonyl)methyl)pyrrolidine-3-carboxylic acid; 2R-(4-methoxyphenyl)-4S(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid
Indication
Disease Entry ICD 11 Status REF
Diabetic nephropathy GB61.Z Phase 3 [1]
Prostate cancer 2C82.0 Withdrawn from market [2] , [3]
Cross-matching ID
PubChem CID
159594
ChEBI ID
CHEBI:135810
CAS Number
CAS 173937-91-2
TTD Drug ID
DMM74PK
VARIDT Drug ID
DR01433
INTEDE Drug ID
DR1899

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DME
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Solid tumour/cancer 2A00-2F9Z Approved [8]
Progesterone DMUY35B Premature labour JB00 Approved [9]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [10]
Estradiol DMUNTE3 Breast cancer 2C60-2C65 Approved [11]
Acetaminophen DMUIE76 Pain MG30-MG3Z Approved [12]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [13]
Etoposide DMNH3PG Solid tumour/cancer 2A00-2F9Z Approved [14]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [15]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [9]
Verapamil DMA7PEW Hypertension BA00-BA04 Approved [16]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Methotrexate DM2TEOL leukaemia 2A60-2B33 Approved [17]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [6]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [18]
Etoposide DMNH3PG Solid tumour/cancer 2A00-2F9Z Approved [19]
Sorafenib DMS8IFC Hepatocellular carcinoma 2C12.02 Approved [18]
Pravastatin DM6A0X7 Hypercholesterolaemia 5C80.0 Approved [20]
Mycophenolate mofetil DMPQAGE Organ transplant rejection NE84 Approved [21]
Atorvastatin DMF28YC Cardiovascular disease BA00-BE2Z Approved [22]
Cerivastatin DMXCM7H Hyperlipidaemia 5C80 Approved [23]
Pitavastatin calcium DM1UJO0 Dyslipidemia 5C80-5C81 Approved [20]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Organic anion transporting polypeptide 1A2 (SLCO1A2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Methotrexate DM2TEOL leukaemia 2A60-2B33 Approved [24]
Dinoprostone DMTYOPD Medical abortion JA00.1Z Approved [25]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [26]
Atorvastatin DMF28YC Cardiovascular disease BA00-BE2Z Approved [27]
Pitavastatin calcium DM1UJO0 Dyslipidemia 5C80-5C81 Approved [28]
Rosuvastatin DMMIQ7G Hypercholesterolaemia 5C80.0 Approved [29]
Saquinavir DMG814N Human immunodeficiency virus infection 1C62 Approved [30]
Enalapril DMNFUZR Hypertension BA00-BA04 Approved [31]
Cholic acid DM7OKQV Peroxisomal disorder 5C57 Approved [32]
Liothyronine DM6IR3P Hypothyroidism 5A00 Approved [33]
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Drug(s) Transported By Organic anion transporting polypeptide 1B3 (SLCO1B3)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Methotrexate DM2TEOL leukaemia 2A60-2B33 Approved [34]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [18]
Etoposide DMNH3PG Solid tumour/cancer 2A00-2F9Z Approved [35]
Diclofenac DMPIHLS Osteoarthritis FA00-FA05 Approved [36]
Sorafenib DMS8IFC Hepatocellular carcinoma 2C12.02 Approved [18]
Pravastatin DM6A0X7 Hypercholesterolaemia 5C80.0 Approved [37]
Mycophenolate mofetil DMPQAGE Organ transplant rejection NE84 Approved [21]
Atorvastatin DMF28YC Cardiovascular disease BA00-BE2Z Approved [23]
Erythromycin DM4K7GQ Bacterial infection 1A00-1C4Z Approved [38]
Cerivastatin DMXCM7H Hyperlipidaemia 5C80 Approved [23]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Targeting Endothelin A receptor (EDNRA)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Bosentan DMIOGBU Pulmonary arterial hypertension BB01.0 Approved [39]
Ambrisentan DMD1QXW Pulmonary arterial hypertension BB01.0 Approved [40]
Macitentan DMP79A1 Cardiovascular disease BA00-BE2Z Approved [41]
LU302146 DMMJVXZ Pulmonary hypertension BB01 Approved [42]
Clazosentan DMQSBX4 Cerebral vasospasm BA85.Z Phase 3 [43]
sparsentan DMMP51W Focal segmental glomerulosclerosis MF8Y Phase 3 [44]
PF-1228305 DMS1EQ7 Pulmonary hypertension BB01 Phase 3 [45]
Darusentan DMN8DQH Hypotension BA20-BA21 Phase 3 [46]
BQ-123 DM0MO8I Pulmonary arterial hypertension BB01.0 Phase 2 [47]
FR139317 DMEL5SV Hypertension BA00-BA04 Phase 2 [48]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Endothelin A receptor (EDNRA) TTKRD0G EDNRA_HUMAN Antagonist [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [5]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [6]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) Main DME DE4LYSA CP3A4_HUMAN Substrate [7]

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 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: 3487).
3 Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
4 Effects of a selective ET(A)-receptor antagonist, atrasentan (ABT-627), in murine models of allergic asthma: demonstration of mouse strain specificity. Clin Sci (Lond). 2002 Aug;103 Suppl 48:367S-370S.
5 Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics. Clin Pharmacol Ther. 2006 Mar;79(3):186-96.
6 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
7 Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics. Clin Pharmacol Ther. 2006 Mar;79(3):186-96.
8 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.
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10 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.
11 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
12 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.
13 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.
14 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
15 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.
16 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.
17 Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
18 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
19 Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
20 The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
21 Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
22 Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
23 FDA Drug Development and Drug Interactions
24 Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
25 Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95.
26 Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
27 Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53.
28 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
29 Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
30 Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Mol Pharm. 2004 Jan 12;1(1):49-56.
31 Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Drug Metab Dispos. 2000 Jul;28(7):801-6.
32 Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82.
33 Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
34 LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
35 Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
36 Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3-mediated drug transport. Drug Metab Dispos. 2011 Jun;39(6):1047-53.
37 Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708.
38 Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
39 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
40 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
41 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
42 Influence of endothelin receptor antagonists on myocardial protein kinase C isoforms in uraemic cardiomyopathy. Clin Sci (Lond). 2002 Aug;103 Suppl 48:276S-279S.
43 Effects of the selective endothelin A (ET(A)) receptor antagonist Clazosentan on cerebral perfusion and cerebral oxygenation following severe subar... Acta Neurochir (Wien). 2007;149(9):911-8; discussion 918.
44 Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
45 Pfizer. Product Development Pipeline. March 31 2009.
46 Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats. J Cardiovasc Pharmacol. 2006 Mar;47(3):456-62.
47 Endothelin in heart failure: a promising therapeutic target Heart. 1997 Feb;77(2):93-4.
48 Reduction of bFGF-induced smooth muscle cell proliferation and endothelin receptor mRNA expression by mevastatin and atorvastatin. Biochem Pharmacol. 2002 Aug 1;64(3):497-505.