Details of the Drug

General Information of Drug (ID: DMP7X6Q)

Drug Name
Rotigotine
Synonyms
Rotigotine; Rotigotine CDS; Rotigotine CDS Patch; SPM 962; SPM-962; (-)-(S)-5,6,7,8-Tetrahydro-6-(propyl(2-(2-thienyl)ethyl)amino)-1-naphthol; Leganto; N 0923; Neupro; (6S)-6-(Propyl(2-(2-thienyl)ethyl)amino)-5,6,7,8-tetrahydro-1-naphthalenol; (6S)-6-[propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol; (S)-6-(propyl(2-(thiophen-2-yl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol; 87T4T8BO2E; 99755-59-6; C19H25NOS; CHEMBL1303; DSSTox_CID_26772; DSSTox_RID_81893; NCGC00168748-01; UNII-87T4T8BO2E
Indication
Disease Entry ICD 11 Status REF
Parkinson disease 8A00.0 Approved [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 315.5
Topological Polar Surface Area (xlogp) 4.9
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 5 - 7 hours [2]
Metabolism
The drug is metabolized via the hepatic [3]
Vd
The volume of distribution (Vd) of drug is 84 L/kg [4]
Chemical Identifiers
Formula
C19H25NOS
IUPAC Name
(6S)-6-[propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol
Canonical SMILES
CCCN(CCC1=CC=CS1)C2CCC3=C(C2)C=CC=C3O
InChI
KFQYTPMOWPVWEJ-INIZCTEOSA-N
InChIKey
1S/C19H25NOS/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21/h3-7,13,16,21H,2,8-12,14H2,1H3/t16-/m0/s1
Cross-matching ID
PubChem CID
59227
ChEBI ID
CHEBI:135351
CAS Number
99755-59-6
DrugBank ID
DB05271
INTEDE ID
DR1446

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [5]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Substrate [6]
Sulfotransferase 1B1 (SULT1B1) DED5UR3 ST1B1_HUMAN Substrate [6]
Sulfotransferase 1A2 (SULT1A2) DERUZL7 ST1A2_HUMAN Substrate [6]
Sulfotransferase 1E1 (SULT1E1) DESTKG6 ST1E1_HUMAN Substrate [6]
Sulfotransferase 1C4 (SULT1C4) DEU3DHN ST1C4_HUMAN Substrate [6]
Sulfotransferase 1A3 (SULT1A3) DEP7E8X ST1A3_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Rotigotine was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
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5 Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67.
6 Identification of the human SULT enzymes involved in the metabolism of rotigotine. J Clin Pharmacol. 2016 Jun;56(6):754-60.
7 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.
8 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
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10 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
11 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.
12 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.
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16 Progestagenic effects of tibolone are target gene-specific in human endometrial cells. J Soc Gynecol Investig. 2006 Sep;13(6):459-65.
17 Tamoxifen-induced adduct formation and cell stress in human endometrial glands. Drug Metab Dispos. 2010 Jan;38(1):200-7.
18 Proposed role of the sulfotransferase/sulfatase pathway in modulating yolk steroid effects. Integr Comp Biol. 2008 Sep;48(3):419-27.
19 Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008 Mar;82(3):155-65.
20 Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents. Curr Drug Metab. 2006 Oct;7(7):745-53.
21 Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1. Phytomedicine. 2001 Nov;8(6):481-8.
22 Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1). Xenobiotica. 2010 Mar;40(3):184-94.
23 Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate. J Endocrinol. 2001 Dec;171(3):525-32.
24 Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate. Biochem Biophys Res Commun. 2005 Sep 23;335(2):417-23.
25 Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Appl Toxicol. 2016 Sep;36(9):1090-4.
26 cDNA cloning and expression of a new form of human aryl sulfotransferase. Int J Biochem Cell Biol. 1996 May;28(5):565-71.
27 SULT 1A3 single-nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: are some athletes at risk of higher urine levels? Drug Test Anal. 2015 Feb;7(2):109-13.
28 Molecular cloning, expression, and functional characterization of novel mouse sulfotransferases. Biochem Biophys Res Commun. 1998 Jun 29;247(3):681-6.
29 Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751. Pharmacogenet Genomics. 2013 Jul;23(7):374-81.
30 Comparison of 2-aminophenol and 4-nitrophenol as in vitro probe substrates for the major human hepatic sulfotransferase, SULT1A1, demonstrates improved selectivity with 2-aminophenol. Biochem Pharmacol. 2007 Jul 15;74(2):352-8.