Identification

Name
Valaciclovir
Accession Number
DB00577  (APRD00697)
Type
Small Molecule
Groups
Approved, Investigational
Description

Valaciclovir (INN) or valacyclovir (USAN) is an antiviral drug used in the management of herpes simplex and herpes zoster (shingles). It is a prodrug, being converted in vivo to aciclovir. It is marketed by GlaxoSmithKline under the trade name Valtrex or Zelitrex. [Wikipedia]

Structure
Thumb
Synonyms
  • L-Valine ester with 9-((2-hydroxyethoxy)methyl)guanine
  • L-Valine, 2-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)ethyl ester
  • Valaciclovirum
  • Valacyclovir
External IDs
256 U 87
Product Ingredients
IngredientUNIICASInChI Key
Valaciclovir HydrochlorideG447S0T1VC124832-27-5ZCDDBUOENGJMLV-QRPNPIFTSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Auro-valacyclovirTablet500 mgOralAuro Pharma Inc2013-05-30Not applicableCanada
Bio-valacyclovirTablet500 mgOralBiomed Pharma2016-04-07Not applicableCanada
Co ValacyclovirTablet1000 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
Co ValacyclovirTablet500 mgOralCobalt Laboratories2010-07-27Not applicableCanada
Dom-valacyclovirTablet500 mgOralDominion Pharmacal2010-07-01Not applicableCanada
Ipg-valacyclovirTablet500 mgOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Jamp-valacyclovirTablet500 mgOralJamp Pharma Corporation2015-10-14Not applicableCanada
Mar-valacyclovirTablet500 mgOralMarcan Pharmaceuticals Inc2015-10-20Not applicableCanada
Mylan-valacyclovirTablet1000 mgOralMylan Pharmaceuticals2010-05-25Not applicableCanada
Mylan-valacyclovirTablet500 mgOralMylan Pharmaceuticals2010-05-25Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-valacyclovirTablet1000 mgOralApotex Corporation2011-10-21Not applicableCanada
Apo-valacyclovirTablet500 mgOralApotex Corporation2008-05-23Not applicableCanada
ValacyclovirTablet, film coated1 g/1OralRanbaxy Inc.2007-01-31Not applicableUs
ValacyclovirCapsule1 g/1OralDirectrx2015-01-01Not applicableUs
ValacyclovirTablet, film coated500 mg/1OralTeva2010-05-24Not applicableUs00093 7258 56 nlmimage10 28301410
ValacyclovirTablet500 mg/1OralOhm Laboratories, Inc.2009-11-25Not applicableUs
ValacyclovirTablet, film coated1 g/1OralA S Medication Solutions2015-05-252017-06-20Us
ValacyclovirTablet, film coated1 g/1OralLucid Pharma Llc2010-05-24Not applicableUs
ValacyclovirTablet, film coated1 g/1OralPd Rx Pharmaceuticals, Inc.2015-05-25Not applicableUs
ValacyclovirTablet1 g/1OralWest Ward Pharmaceutical2010-05-242019-01-30Us
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ValtrexTablet, film coated1 g/1OralA S Medication Solutions2002-08-12Not applicableUs
International/Other Brands
Bagovir (Bago) / Cycloval (GMP) / Mitanga (Aversi) / Ovalac (Beximco) / Pervioral (Royal Pharma) / Revira (Square) / Vacyless (Yung Shin) / Vadiral (Gynopharm) / Valdacir (Actavis) / Valotix (Rowex) / Valvir (Soho) / Valztrex (Northia) / Viramixal (Panalab) / Viropel (Pelpharma) / Vociflon (Pharmathen) / Zelitrex (GlaxoSmithKline) / Zelivire (Ranbaxy)
Categories
UNII
MZ1IW7Q79D
CAS number
124832-26-4
Weight
Average: 324.3357
Monoisotopic: 324.154603158
Chemical Formula
C13H20N6O4
InChI Key
HDOVUKNUBWVHOX-QMMMGPOBSA-N
InChI
InChI=1S/C13H20N6O4/c1-7(2)8(14)12(21)23-4-3-22-6-19-5-16-9-10(19)17-13(15)18-11(9)20/h5,7-8H,3-4,6,14H2,1-2H3,(H3,15,17,18,20)/t8-/m0/s1
IUPAC Name
2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl (2S)-2-amino-3-methylbutanoate
SMILES
CC(C)[[email protected]](N)C(=O)OCCOCN1C=NC2=C1NC(N)=NC2=O

Pharmacology

Indication

For the treatment or suppression of cold sores (herpes labialis), herpes zoster (shingles), genital herpes in immunocompetent individuals, and recurrent genital herpes in HIV-infected individuals.

Structured Indications
Pharmacodynamics

Valaciclovir (INN) or Valacyclovir (USAN) is a prodrug and synthetic purine nucleoside analogue with inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Valaciclovir is almost completely converted to acyclovir and L-valine. The inhibitory activity of valaciclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, which is then converted into acyclovir diphosphate and triphosphate by cellular enzymes. Acyclovir is selectively converted to the active triphosphate form by cells infected with herpes viruses.

Mechanism of action

Valaciclovir is phosphorylated by viral thymidine kinase to acyclovir triphosphate (the active metabolite) which then inhibits herpes viral DNA replication by competitive inhibition of viral DNA polymerase, and by incorporation into and termination of the growing viral DNA chain. When used as a substrate for viral DNA polymerase, acyclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where acyclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand.

TargetActionsOrganism
AThymidine kinase
inducer
HHV-1
ADNA polymerase catalytic subunit
inhibitor
HHV-1
Absorption

After oral administration, valaciclovir hydrochloride is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of acyclovir after administration of valaciclovir is 54.5% ± 9.1%.

Volume of distribution
Not Available
Protein binding

13-18%

Metabolism

Valaciclovir is rapidly and almost entirely (~99%) converted to the active compound, acyclovir, and L-valine by first-pass intestinal and hepatic metabolism by enzymatic hydrolysis. Neither valaciclovir nor acyclovir is metabolized by cytochrome P450 enzymes.

Route of elimination

Acyclovir accounted for 89% of the radioactivity excreted in the urine.

Half life

2.5-3.3 hours

Clearance
  • Renal cl=255 +/-  86 mL/min [healthy]
  • apparent cl=86.3 +/- 21.3 mL/min/1.73 m2 [dialysis patients]
  • apparent cl=679.16 +/- 162.76 mL/min/1.73 m2 [healthy]
Toxicity

Adverse effects of overexposure might include headache and nausea.

Affected organisms
  • Human Herpes Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
FoscarnetFoscarnet may increase the nephrotoxic activities of Valaciclovir.Approved
Mycophenolic acidThe serum concentration of Mycophenolic acid can be increased when it is combined with Valaciclovir.Approved
Tenofovir disoproxilValaciclovir may decrease the excretion rate of Tenofovir disoproxil which could result in a higher serum level.Approved, Investigational
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Valaciclovir.Approved
ZidovudineValaciclovir may increase the central nervous system depressant (CNS depressant) activities of Zidovudine.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Valaciclovir.Approved
Food Interactions
Not Available

References

Synthesis Reference

Marina Etinger, "Synthesis and purification of valacyclovir." U.S. Patent US20030153757, issued August 14, 2003.

US20030153757
General References
  1. O'Brien JJ, Campoli-Richards DM: Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1989 Mar;37(3):233-309. [PubMed:2653790]
  2. Umapathy NS, Ganapathy V, Ganapathy ME: 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. [PubMed:15290873]
External Links
Human Metabolome Database
HMDB14716
KEGG Drug
D00398
KEGG Compound
C07184
PubChem Compound
60773
PubChem Substance
46508197
ChemSpider
54770
BindingDB
50162073
ChEBI
35854
ChEMBL
CHEMBL1349
Therapeutic Targets Database
DAP000643
PharmGKB
PA451839
HET
TXC
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Valaciclovir
ATC Codes
J05AB11 — Valaciclovir
AHFS Codes
  • 08:18.32 — Nucleosides and Nucleotides
PDB Entries
4aql
MSDS
Download (29.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCancer, Breast / Cancer, Ovarian / Lung Cancers / Malignant Pleural Effusions / Mesothelioma1
1Active Not RecruitingTreatmentHerpes Simplex Virus 21
1Active Not RecruitingTreatmentMalignant Gliomas / Recurrent Ependymoma1
1CompletedNot AvailableHealthy Volunteers5
1CompletedNot AvailableHerpes Simplex Virus Infection / Varicella Zoster Virus Infection1
1CompletedTreatmentAdenocarcinoma of the Pancreas / Malignant Neoplasm of Pancreas1
1CompletedTreatmentAnaplastic Astrocytoma (AA) / Glioblastoma Multiforme / Malignant Gliomas1
1CompletedTreatmentChronic Hepatitis C Infection1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHerpes Simplex1
1CompletedTreatmentShingles / Transplantation, Bone Marrow1
1TerminatedNot AvailableSafety of ASP21511
1Unknown StatusPreventionHerpes Simplex1
1Unknown StatusTreatmentHepatitis C Virus Infection / Herpesvirus 2, Human / Infection NOS1
1WithdrawnTreatmentChickenpox / Herpes Simplex / Human Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentInfectious Mononucleosis1
1, 2RecruitingTreatmentProstatic Neoplasms1
2Active Not RecruitingBasic ScienceANCA Associated Vasculitis / CMV Infections1
2Active Not RecruitingTreatmentSchizophrenic Disorders1
2Active Not RecruitingTreatmentWaldenstrom's Macroglobulinemia (WM)1
2CompletedPreventionCritical Illness1
2CompletedPreventionHerpes simplex of the genitals / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentAnaplastic Astrocytoma (AA) / Glioblastoma Multiforme / Malignant Gliomas1
2CompletedTreatmentChronic Hepatitis C Infection1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
2CompletedTreatmentHerpes Labialis1
2CompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHerpes Zoster2
2CompletedTreatmentHerpes Zoster / Shingles1
2CompletedTreatmentHerpes simplex of the genitals1
2CompletedTreatmentNeoplasms1
2CompletedTreatmentPsychosis1
2CompletedTreatmentPsychosis / Schizophrenic Disorders1
2Not Yet RecruitingTreatmentAlzheimer's Disease (AD) / Herpes simplex 1 / Herpes Simplex 21
2RecruitingPreventionEpstein-Barr Virus Infections / Infections, Cytomegalovirus / Transplantation Infection1
2RecruitingTreatmentAlzheimer's Disease (AD) / Herpes Simplex / Mild Cognitive Impairment (MCI)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
2RecruitingTreatmentHerpetic Gingivostomatitis1
2RecruitingTreatmentLung Squamous Cell Carcinoma Stage IV / Nonsquamous Nonsmall Cell Neoplasm of Lung1
2RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer / Metastatic Triple-negative Breast Cancer1
2TerminatedPreventionGenital Herpes1
2Unknown StatusTreatmentBipolar Disorder (BD)1
2Unknown StatusTreatmentHerpes Zoster / Postherpetic Neuralgia1
2Unknown StatusTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
2, 3RecruitingPreventionCytomegalovirus Congenital Infection1
2, 3RecruitingTreatmentProstate Cancer1
3Active Not RecruitingTreatmentHerpes Simplex Type II / Human Immunodeficiency Virus (HIV) Infections1
3CompletedPreventionHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections / Sexually Transmitted Disease (STD)2
3CompletedSupportive CareCancers1
3CompletedTreatmentGenital Herpes1
3CompletedTreatmentHerpes Simplex1
3CompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHerpes Zoster1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infections, Cytomegalovirus1
3CompletedTreatmentInflammation, Brain1
3RecruitingPreventionHerpes Zoster / Postherpetic Neuralgia / Shingles1
3RecruitingTreatmentProstate Cancer1
3Unknown StatusTreatmentHerpes Simplex / Herpes simplex of the genitals / Human Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHerpes Simplex Virus Infection / Varicella Zoster Virus Infection1
4CompletedPreventionHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentBell's Palsy1
4CompletedTreatmentGenital Herpes2
4CompletedTreatmentGenital Herpes / Herpes Labialis1
4CompletedTreatmentGenital Herpes / Herpes simplex of the genitals1
4CompletedTreatmentGenital Herpes / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentGenital Herpes / Infections, Herpesviridae1
4CompletedTreatmentHerpes Simplex Infection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentVirus Diseases1
4RecruitingTreatmentVaricella-zoster virus acute retinal necrosis1
4TerminatedNot AvailableGenital Herpes / Human Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentInfections, Cytomegalovirus / Viral Diseases1
Not AvailableCompletedNot AvailableHealthy Volunteers2
Not AvailableCompletedNot AvailableVaricella1
Not AvailableCompletedPreventionHerpes Simplex Type Two Infection / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentBell's Palsy1
Not AvailableCompletedTreatmentGenital Herpes / Herpes Zoster / Shingles2
Not AvailableCompletedTreatmentHSV-2 / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections3
Not AvailableCompletedTreatmentHerpes Zoster / Immunologic Deficiency Syndromes1
Not AvailableCompletedTreatmentHerpes Zoster / Post-Herpetic Neuralgia (PHN)1
Not AvailableWithdrawnBasic ScienceHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableWithdrawnPreventionBacterial Vaginosis (BV) / Herpes Simplex Virus Type II1

Pharmacoeconomics

Manufacturers
  • Aurobindo pharma ltd
  • Dr reddys laboratories ltd
  • Matrix laboratories ltd
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • Wockhardt ltd
  • Glaxosmithkline
Packagers
Dosage forms
FormRouteStrength
TabletOral1000 mg
CapsuleOral1 g/1
TabletOral1 g/1
TabletOral500 mg/1
Tablet, film coatedOral500 mg/1
TabletOral1000 mg/1
Tablet, coatedOral500 mg/1
Tablet, film coatedOral1 g/1
TabletOral500 mg
Prices
Unit descriptionCostUnit
Valtrex 1 gm tablet14.62USD tablet
Valtrex 1 gm caplet14.06USD caplet
Valacyclovir HCl 1 gm tablet12.87USD tablet
Valtrex 500 mg tablet8.36USD tablet
Valacyclovir HCl 500 mg tablet7.35USD tablet
Valtrex (Caplet) 500 mg Tablet3.82USD tablet
Apo-Valacyclovir (Caplet) 500 mg Tablet2.14USD tablet
Pms-Valacyclovir (Caplet) 500 mg Tablet2.14USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4957924No1992-12-232009-12-23Us
CA2243237No2008-09-022017-01-17Canada
CA1340083No1998-10-132015-10-13Canada
US5879706Yes1996-07-192016-07-19Us
US6107302Yes1996-07-192016-07-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-0.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility3.55 mg/mLALOGPS
logP-0.84ALOGPS
logP-0.45ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)8.1ChemAxon
pKa (Strongest Basic)7.36ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area146.85 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity80.63 m3·mol-1ChemAxon
Polarizability31.96 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9475
Blood Brain Barrier+0.9389
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.7487
P-glycoprotein inhibitor INon-inhibitor0.7467
P-glycoprotein inhibitor IINon-inhibitor0.9586
Renal organic cation transporterNon-inhibitor0.8553
CYP450 2C9 substrateNon-substrate0.8941
CYP450 2D6 substrateNon-substrate0.8244
CYP450 3A4 substrateSubstrate0.5571
CYP450 1A2 substrateNon-inhibitor0.8155
CYP450 2C9 inhibitorNon-inhibitor0.8734
CYP450 2D6 inhibitorNon-inhibitor0.8797
CYP450 2C19 inhibitorNon-inhibitor0.7944
CYP450 3A4 inhibitorNon-inhibitor0.9351
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8373
Ames testNon AMES toxic0.6139
CarcinogenicityNon-carcinogens0.9345
BiodegradationNot ready biodegradable0.899
Rat acute toxicity2.2217 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9427
hERG inhibition (predictor II)Non-inhibitor0.7378
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-1910000000-3db14f76ba496cea0d81

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid esters
Alternative Parents
Valine and derivatives / 6-oxopurines / Hypoxanthines / Pyrimidones / Aminopyrimidines and derivatives / Fatty acid esters / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Carboxylic acid esters
show 7 more
Substituents
Alpha-amino acid ester / Valine or derivatives / 6-oxopurine / Hypoxanthine / Imidazopyrimidine / Purine / Aminopyrimidine / Pyrimidone / Fatty acid ester / N-substituted imidazole
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
L-valinyl ester (CHEBI:35854)

Targets

Kind
Protein
Organism
HHV-1
Pharmacological action
Yes
Actions
Inducer
General Function
Thymidine kinase activity
Specific Function
In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate the...
Gene Name
TK
Uniprot ID
Q9QNF7
Uniprot Name
Thymidine kinase
Molecular Weight
40896.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Teh BS, Ayala G, Aguilar L, Mai WY, Timme TL, Vlachaki MT, Miles B, Kadmon D, Wheeler T, Caillouet J, Davis M, Carpenter LS, Lu HH, Chiu JK, Woo SY, Thompson T, Aguilar-Cordova E, Butler EB: Phase I-II trial evaluating combined intensity-modulated radiotherapy and in situ gene therapy with or without hormonal therapy in treatment of prostate cancer-interim report on PSA response and biopsy data. Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1520-9. [PubMed:15050332]
  4. Satoh T, Teh BS, Timme TL, Mai WY, Gdor Y, Kusaka N, Fujita T, Pramudji CK, Vlachaki MT, Ayala G, Wheeler T, Amato R, Miles BJ, Kadmon D, Butler EB, Thompson TC: Enhanced systemic T-cell activation after in situ gene therapy with radiotherapy in prostate cancer patients. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):562-71. [PubMed:15145177]
  5. Hinata N, Shirakawa T, Terao S, Goda K, Tanaka K, Yamada Y, Hara I, Kamidono S, Fujisawa M, Gotoh A: Progress report on phase I/II clinical trial of Ad-OC-TK plus VAL therapy for metastatic or locally recurrent prostate cancer: Initial experience at Kobe University. Int J Urol. 2006 Jun;13(6):834-7. [PubMed:16834676]
Kind
Protein
Organism
HHV-1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding pro...
Gene Name
Not Available
Uniprot ID
P04293
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
136419.66 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Scott GM, Ng HL, Morton CJ, Parker MW, Rawlinson WD: Murine cytomegalovirus resistant to antivirals has genetic correlates with human cytomegalovirus. J Gen Virol. 2005 Aug;86(Pt 8):2141-51. [PubMed:16033961]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH: Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5. [PubMed:9610386]
  2. Han H, de Vrueh RL, Rhie JK, Covitz KM, Smith PL, Lee CP, Oh DM, Sadee W, Amidon GL: 5'-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm Res. 1998 Aug;15(8):1154-9. [PubMed:9706043]
  3. Balimane PV, Tamai I, Guo A, Nakanishi T, Kitada H, Leibach FH, Tsuji A, Sinko PJ: Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir. Biochem Biophys Res Commun. 1998 Sep 18;250(2):246-51. [PubMed:9753615]
  4. Sawada K, Terada T, Saito H, Hashimoto Y, Inui KI: Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2. J Pharmacol Exp Ther. 1999 Nov;291(2):705-9. [PubMed:10525090]
  5. Balimane P, Sinko P: Effect of ionization on the variable uptake of valacyclovir via the human intestinal peptide transporter (hPepT1) in CHO cells. Biopharm Drug Dispos. 2000 Jul;21(5):165-74. [PubMed:11180195]
  6. Guo A, Hu P, Balimane PV, Leibach FH, Sinko PJ: Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line. J Pharmacol Exp Ther. 1999 Apr;289(1):448-54. [PubMed:10087037]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peptide:proton symporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name
SLC15A2
Uniprot ID
Q16348
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
References
  1. Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH: Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5. [PubMed:9610386]
  2. Sawada K, Terada T, Saito H, Hashimoto Y, Inui KI: Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2. J Pharmacol Exp Ther. 1999 Nov;291(2):705-9. [PubMed:10525090]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. [PubMed:10945832]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Neurotransmitter:sodium symporter activity
Specific Function
Mediates the uptake of a broad range of neutral and cationic amino acids (with the exception of proline) in a Na(+)/Cl(-)-dependent manner.
Gene Name
SLC6A14
Uniprot ID
Q9UN76
Uniprot Name
Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)
Molecular Weight
72152.145 Da
References
  1. Umapathy NS, Ganapathy V, Ganapathy ME: 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. [PubMed:15290873]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Bile acid:sodium symporter activity
Specific Function
Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.
Gene Name
SLC10A2
Uniprot ID
Q12908
Uniprot Name
Ileal sodium/bile acid cotransporter
Molecular Weight
37713.405 Da
References
  1. Tolle-Sander S, Lentz KA, Maeda DY, Coop A, Polli JE: Increased acyclovir oral bioavailability via a bile acid conjugate. Mol Pharm. 2004 Jan 12;1(1):40-8. [PubMed:15832499]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33