Details of the Drug

General Information of Drug (ID: DMBKVJY)

Drug Name
PMEA
Synonyms
ADEFOVIR; 106941-25-7; PMEA; ((2-(6-Amino-9H-purin-9-yl)ethoxy)methyl)phosphonic acid; 9-(2-Phosphonylmethoxyethyl)adenine; GS-0393; GS 0393; GS 393; 9-(2-(Phosphonomethoxy)ethyl)adenine; N-(2-Phosphonylmethoxyethyl)adenine; DRG-0156; UNII-6GQP90I798; C8H12N5O4P; HSDB 8079; CHEMBL484; 2-(6-aminopurin-9-yl)ethoxymethylphosphonic acid; BRN 3561094; {[2-(6-Amino-9h-Purin-9-Yl)ethoxy]methyl}phosphonic Acid; N-(2-Phophonomethoxyethyl-2,6-diaminopurine); Phosphonic acid, [[2-(6-amino-9H-purin-9-yl)ethoxy]methyl]-; 6GQP90I798
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 273.19
Logarithm of the Partition Coefficient (xlogp) -2
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
Elimination
45% of drug is excreted from urine in the unchanged form [2]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.4287 micromolar/kg/day [3]
Water Solubility
The ability of drug to dissolve in water is measured as 0.4 mg/mL [2]
Chemical Identifiers
Formula
C8H12N5O4P
IUPAC Name
2-(6-aminopurin-9-yl)ethoxymethylphosphonic acid
Canonical SMILES
C1=NC(=C2C(=N1)N(C=N2)CCOCP(=O)(O)O)N
InChI
InChI=1S/C8H12N5O4P/c9-7-6-8(11-3-10-7)13(4-12-6)1-2-17-5-18(14,15)16/h3-4H,1-2,5H2,(H2,9,10,11)(H2,14,15,16)
InChIKey
SUPKOOSCJHTBAH-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
60172
ChEBI ID
CHEBI:2469
CAS Number
106941-25-7
TTD ID
D00UUM

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Herpes simplex virus DNA polymerase UL30 (HSV UL30) TTIU7X1 DPOL_HHV11 Inhibitor [1]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Regulation of Drug Effects [4]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Gene/Protein Processing [5]
Methylmalonyl-CoA mutase, mitochondrial (MMUT) OTBBBV70 MUTA_HUMAN Gene/Protein Processing [6]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Drug Response [7]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Drug Response [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Herpes simplex virus-specified DNA polymerase is the target for the antiviral action of 9-(2-phosphonylmethoxyethyl)adenine. J Biol Chem. 1991 Jan 5;266(1):238-44.
2 BDDCS applied to over 900 drugs
3 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
4 The human multidrug resistance protein 4 (MRP4, ABCC4): functional analysis of a highly polymorphic gene. J Pharmacol Exp Ther. 2008 Jun;325(3):859-68. doi: 10.1124/jpet.108.136523. Epub 2008 Mar 25.
5 Inhibition of human liver microsomal cytochrome P450 activities by adefovir and tenofovir. Xenobiotica. 2006 Dec;36(12):1165-77.
6 Gene induction for the treatment of methylmalonic aciduria. J Gene Med. 2009 Apr;11(4):361-9. doi: 10.1002/jgm.1297.
7 Intracellular concentrations determine the cytotoxicity of adefovir, cidofovir and tenofovir. Toxicol In Vitro. 2015 Feb;29(1):251-8. doi: 10.1016/j.tiv.2014.10.019.
8 Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates. Toxicology. 2013 Sep 15;311(3):135-46. doi: 10.1016/j.tox.2013.07.004. Epub 2013 Jul 13.