Details of the Drug

General Information of Drug (ID: DMC40UY)

Drug Name
Tenofovir disoproxil
Synonyms
Tenofovir disoproxil; PMPA prodrug; Bis(POC)PMPA; Tenofovir (Disoproxil); UNII-F4YU4LON7I; 9-((R)-2-((Bis(((isopropoxycarbonyl)oxy)methoxy)phosphinyl)methoxy)propyl)adenine; F4YU4LON7I; CHEBI:63717; tenofovir bis(isopropyloxycarbonyloxymethyl) ester; Tenofovir Disoproxil Fumarate; [[(1R)-2-(6-aminopurin-9-yl)-1-methyl-ethoxy]methyl-(isopropoxycarbonyloxymethoxy)phosphoryl]oxymethyl isopropyl carbonate
Indication
Disease Entry ICD 11 Status REF
Hepatitis B virus infection 1E51.0 Phase 4 [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski):
3		 Molecular Weight 519.4
Topological Polar Surface Area Not Available
Rotatable Bond Count 17
Hydrogen Bond Donor Count 1
Hydrogen Bond Acceptor Count 14
ADMET Property
Clearance
The renal clearance of drug is 160 mL/h/kg [2]
Elimination
Following IV administration of tenofovir, approximately 70C80% of the dose is recovered in the urine as unchanged tenofovir within 72 hours of dosing [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 17 hours [3]
Metabolism
The drug is metabolized via the constitutively expressed enzymes in the cell [4]
Vd
The volume of distribution (Vd) of drug is 1.3 +/- 0.6 L/kg [2]
Chemical Identifiers
Formula
C19H30N5O10P
IUPAC Name
[[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate
Canonical SMILES
CC(C)OC(=O)OCOP(=O)(COC(C)CN1C=NC2=C(N=CN=C21)N)OCOC(=O)OC(C)C
InChI
InChI=1S/C19H30N5O10P/c1-12(2)33-18(25)28-9-31-35(27,32-10-29-19(26)34-13(3)4)11-30-14(5)6-24-8-23-15-16(20)21-7-22-17(15)24/h7-8,12-14H,6,9-11H2,1-5H3,(H2,20,21,22)/t14-/m1/s1
InChIKey
JFVZFKDSXNQEJW-CQSZACIVSA-N
Cross-matching ID
PubChem CID
5481350
ChEBI ID
CHEBI:63717
CAS Number
201341-05-1
DrugBank ID
DB00300
VARIDT ID
DR01689

Molecular Interaction Atlas of This Drug


Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 ClinicalTrials.gov (NCT03485534) Evaluate the Efficacy and Safety to Tenofovir Disoproxil in Chronic Hepatitis B Patients
2 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
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.
4 Fromenty B, Freneaux E, Labbe G, Deschamps D, Larrey D, Letteron P, Pessayre D: Tianeptine, a new tricyclic antidepressant metabolized by beta-oxidation of its heptanoic side chain, inhibits the mitochondrial oxidation of medium and short chain fatty acids in mice. Biochem Pharmacol. 1989 Nov 1;38(21):3743-51.
5 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
6 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
7 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
8 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
9 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
10 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
11 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.