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

General Information of Drug (ID: DMS2IUH)

• Drug Name: Valganciclovir Drug Info
• Synonyms: Cymeval; RS 79070; RO1079070/194; Valcyte (TN); Valganciclovir (INN); Valganciclovir (Oral); Valganciclovir [INN:BAN]; L-Valine, ester with ganciclovir; [2-[(2-amino-6-oxo-3H-purin-9-yl)methoxy]-3-hydroxypropyl] (2S)-2-amino-3-methylbutanoate; L-Valine, 2-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-3-hydroxypropyl ester; 5-Amino-3-[1-(hydroxymethyl)-2-(L-valyloxy)ethoxymethyl]-6,7-dihydro-3H-imidazo[4,5-d]pyrimidin-7-one

Indication

Disease Entry	ICD 11	Status	REF
Virus infection	1A24-1D9Z	Approved	[1]

• Therapeutic Class: Antiviral Agents
• Cross-matching ID:
  PubChem CID: 135413535
  ChEBI ID: CHEBI:63635
  CAS Number: CAS 175865-60-8
  TTD Drug ID: DMS2IUH
  VARIDT Drug ID: DR00404
  ACDINA Drug ID: D00716

Molecule-Related Drug Atlas

Drug(s) Targeting Herpes simplex virus DNA polymerase UL30 (HSV UL30)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[5]
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[6]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[7]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[8]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[6]
Penciclovir	DMOUMDV	Herpes simplex labialis	1F00.01	Approved	[9]
Famciclovir	DMJHLSD	Meniere disease	AB31.0	Approved	[10]
Valacyclovir Hydrochloride	DM5I1CE	Herpes simplex virus infection	1F00	Approved	[6]
Foscavir	DM9KJLZ	Cytomegalovirus retinitis	9B72.00	Approved	[2]
Netivudine	DMTKRY1	Virus infection	1A24-1D9Z	Phase 3	[11]

Drug(s) Transported By Peptide transporter 1 (SLC15A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[12]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[13]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[14]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[15]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[16]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[17]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[18]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[13]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[15]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[15]

Drug(s) Transported By Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[19]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[19]
Levacecarnine hci	DMJBOCR	Cognitive impairment	6D71	Approved	[20]
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[21]
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[22]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[23]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[24]
D-Serine	DM3YH4I	N. A.	N. A.	Phase 4	[25]
L-threonine	DMFHTBX	Discovery agent	N.A.	Investigative	[25]

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	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)	DTW7AE3	AAAT_HUMAN	Substrate	[3]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[4]

References

• [1] 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: 4716).
• [2] Drug targets in cytomegalovirus infection. Infect Disord Drug Targets. 2009 Apr;9(2):201-22.
• [3] Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10.
• [4] Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000 Jun;89(6):781-9.
• [5] Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Application of real time polymerase chain reaction to the diagnosis and treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2009 Feb;30(2):77-81.
• [8] Extensive oral shedding of human herpesvirus 8 in a renal allograft recipient. Oral Microbiol Immunol. 2009 Apr;24(2):109-15.
• [9] Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66.
• [10] Penciclovir cream--improved topical treatment for herpes simplex infections. Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):214-8.
• [11] Current pharmacological approaches to the therapy of varicella zoster virus infections: a guide to treatment. Drugs. 1999 Feb;57(2):187-206.
• [12] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [13] Peptide transporter substrate identification during permeability screening in drug discovery: comparison of transfected MDCK-hPepT1 cells to Caco-2 cells. Arch Pharm Res. 2007 Apr;30(4):507-18.
• [14] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [15] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [16] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [17] Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
• [18] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [19] Amino Acid Transporter ATB0,+ as a delivery system for drugs and prodrugs. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):357-64.
• [20] A polarized localization of amino acid/carnitine transporter B(0,+) (ATB(0,+)) in the blood-brain barrier. Biochem Biophys Res Commun. 2008 Nov 14;376(2):267-70.
• [21] Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+). Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1046-53.
• [22] High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes. Neurochem Int. 2006 May-Jun;48(6-7):611-5.
• [23] Transport of amino acid-based prodrugs by the Na+- and Cl(-) -coupled amino acid transporter ATB0,+ and expression of the transporter in tissues amenable for drug delivery. J Pharmacol Exp Ther. 2004 Mar;308(3):1138-47.
• [24] Functional regulation of Na+-dependent neutral amino acid transporter ASCT2 by S-nitrosothiols and nitric oxide in Caco-2 cells. FEBS Lett. 2005 Apr 25;579(11):2499-506.
• [25] D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. PLoS One. 2016 Jun 7;11(6):e0156551.