GANCICLOVIR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H13N5O4
Molecular Weight	255.2306
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1

InChI

InChIKey=IRSCQMHQWWYFCW-UHFFFAOYSA-N

InChI=1S/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16305999http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/2177317 | https://www.ncbi.nlm.nih.gov/pubmed/3265058 | https://adisinsight.springer.com/drugs/800001059http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/monograph/valganciclovir-hydrochloride.html | http://www.rxlist.com/valcyte-drug/indications-dosage.htm

Ganciclovir is a synthetic acyclic nucleoside analogue of 2'-deoxyguanosine active against cytomegalovirus. Ganciclovir has been shown to be active against cytomegalovirus (CMV) and herpes simplex virus (HSV) in humans. To achieve anti-CMV activity, ganciclovir is phosphorylated first to the monophosphate form by a CMV-encoded (UL97 gene) protein kinase homologue, then to the di- and triphosphate forms by cellular kinases. Ganciclovir triphosphate concentrations may be 100-fold greater in CMV-infected than in uninfected cells, indicating preferential phosphorylation in infected cells. Ganciclovir triphosphate, once formed, persists for days in the CMV-infected cell. Ganciclovir triphosphate is believed to inhibit viral DNA synthesis by (1) competitive inhibition of viral DNA polymerases; and (2) incorporation into viral DNA, resulting in eventual termination of viral DNA elongation. Ganciclovir is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS) and for the treatment of acute herpetic keratitis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA polymerase catalytic subunit 14 Target ID: P08546 Gene ID: NA Gene Symbol: UL54 Target Organism: Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) Sources: http://cid.oxfordjournals.org/content/35/7/866.full.pdf+html	Antagonist 2778
Human herpesvirus 5 DNA polymerase 18 Target ID: CHEMBL3414 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdf	Inhibitor 8297		0.08 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2578
Acute herpetic keratitis 8 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022211lbl.pdf	Primary	Approved 8429	ZIRGAN Approved Use ZIRGAN is a topical ophthalmic antiviral that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). Launch Date 1995
Cytomegalovirus retinitis 16 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdf	Primary	Approved 8429	CYTOVENE Approved Use CYTOVENE-IV is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). CYTOVENE-IV is also indicated for the prevention of CMV disease in transplant recipients at risk for CMV disease. Launch Date 1994
Cytomegalovirus retinitis 16 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdf	Primary	Approved 8429	VALCYTE Approved Use VALCYTE is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Launch Date 2001
Cytomegalovirus infectious disease in kidney, heart, and kidney-pancreas transplantation 8 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdf	Primary	Approved 8429	VALCYTE Approved Use VALCYTE is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk Launch Date 2001

C_max

Value	Dose	Co-administered	Analyte	Population
4.8 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10747829	1 g 3 times / day multiple, oral dose: 1 g route of administration: Oral experiment type: MULTIPLE co-administered:		GANCICLOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
13.3 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		GANCICLOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
35.4 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10747829	1 g 3 times / day multiple, oral dose: 1 g route of administration: Oral experiment type: MULTIPLE co-administered:		GANCICLOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
53.8 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		GANCICLOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936	5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		GANCICLOVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1000 mg 6 times / day multiple, oral Highest studied dose Dose: 1000 mg, 6 times / day Route: oral Route: multiple Dose: 1000 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7769276/	unhealthy, 37.4 n = 19 Health Status: unhealthy Condition: AIDS Age Group: 37.4 Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/7769276/	Sources: https://pubmed.ncbi.nlm.nih.gov/7769276/
2000 mg 3 times / day multiple, oral Highest studied dose Dose: 2000 mg, 3 times / day Route: oral Route: multiple Dose: 2000 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7769276/	unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/7769276/	Other AEs: Neutropenia, Thrombocytopenia... Other AEs: Neutropenia (18%) Thrombocytopenia (4%) Anemia (severe, 4%) Renal impairment (4%) Sources: https://pubmed.ncbi.nlm.nih.gov/7769276/
50 mg/kg 3 times / day multiple, oral Highest studied dose Dose: 50 mg/kg, 3 times / day Route: oral Route: multiple Dose: 50 mg/kg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11069232/	unhealthy, 7.4 years (range: 0.5-16.9 years) n = 36 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 7.4 years (range: 0.5-16.9 years) Population Size: 36 Sources: https://pubmed.ncbi.nlm.nih.gov/11069232/	Other AEs: Neutropenia... Other AEs: Neutropenia (22%) Sources: https://pubmed.ncbi.nlm.nih.gov/11069232/
5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdf	unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdf	Other AEs: Fever, Infection... Other AEs: Fever (48%) Infection (13%) Chills (10%) Sepsis (15%) Diarrhea (44%) Anorexia (14%) Vomiting (13%) Leukopenia (41%) Anemia (25%) Thrombocytopenia (6%) Neuropathy (9%) Sweating (12%) Pruritus (5%) Catheter infection (9%) Catheter sepsis (8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			supressor 10

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	MATE1 135 MATE2 96 OCT1 327 OAT1 326 OAT2 115 OAT3 339 OCT2 355 P-gp 1537 MRP4 77

Drug as victim

Target	Modality	Activity
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28179375/ \| https://pubmed.ncbi.nlm.nih.gov/22190696/	no
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22190696/	no
MATE1 135	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MATE2 96	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17509534/	yes
MRP4 77	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12105214/	yes
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/ \| https://pubmed.ncbi.nlm.nih.gov/28179375/ \| https://pubmed.ncbi.nlm.nih.gov/22190696/	yes
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28179375/ \| https://pubmed.ncbi.nlm.nih.gov/22190696/	yes
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11861798/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20969937/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	supressor 10 Sources: https://pubmed.ncbi.nlm.nih.gov/22777050/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:465284	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:465284
ChemicalBook	CB6203364	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6203364
MolPort	MolPort-000-758-398	https://www.molport.com/shop/molecule-link/MolPort-000-758-398
MolPort	MolPort-002-507-301	https://www.molport.com/shop/molecule-link/MolPort-002-507-301
MolPort	MolPort-006-167-681	https://www.molport.com/shop/molecule-link/MolPort-006-167-681
Selleck Chemicals	ganciclovir	http://www.selleckchem.com/products/ganciclovir.html
ZINC	ZINC000000001505	http://zinc15.docking.org/substances/ZINC000000001505
eMolecules	31410312	https://www.emolecules.com/cgi-bin/more?vid=31410312
eMolecules	538661	https://www.emolecules.com/cgi-bin/more?vid=538661

PubMed

Title	Date	PubMed
Structure-activity relationships of L-dioxolane uracil nucleosides as anti-Epstein Barr virus agents.	1999 Jun 17	10377226
Risk for cytomegalovirus disease in patients receiving polymerase chain reaction-based preemptive antiviral therapy after allogeneic stem cell transplantation depends on transplantation modality.	2001 Apr 1	11286223
Genetic risks of antiviral nucleoside analogues--a survey.	2001 Feb	11248359
Conditional abatement of tissue fibrosis using nucleoside analogs to selectively corrupt DNA replication in transgenic fibroblasts.	2001 Feb	11237671
Coexistent cutaneous Aspergillus and cytomegalovirus infection in a liver transplant recipient.	2001 Feb	11174418
Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes.	2001 Feb 15	11159510
A tightly regulated immortalized human fetal hepatocyte cell line to develop a bioartificial liver.	2001 Feb-Mar	11267582
Ganciclovir prophylaxis for cytomegalovirus infection in simultaneous kidney-pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone.	2001 Feb-Mar	11267516
Antiviral drugs in chronic hepatitis B: review and meta-analysis.	2001 Jan	11204937
In vitro effects of antiviral agents on human keratocytes.	2001 Jan	11189008
Management of complications associated with totally implantable ports in patients with AIDS.	2001 Jan	11177583
The real danger of lamivudine-resistant hepatitis B virus infection in the immunocompromised host.	2001 Mar	11244173
Frosted branch angiitis in a child with HIV infection.	2001 Mar	11239884

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Unknown

Name

Type

Language

GANCICLOVIR

Official Name

English

BW 759U

Code

English

GANCICLOVIR [HSDB]

Common Name

English

GANCICLOVIR [EP IMPURITY]

Common Name

English

GANCICLOVIR [EMA EPAR]

Common Name

English

9-[[2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine

Systematic Name

English

Ganciclovir [WHO-DD]

Common Name

English

VALGANCICLOVIR HYDROCHLORIDE IMPURITY A [USP IMPURITY]

Common Name

English

GANCICLOVIR [USAN]

Common Name

English

GANCICLOVIR [USP MONOGRAPH]

Common Name

English

6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-((2-HYDROXY-1-(HYDROXYMETHYL)ETHOXY)METHYL)-

Systematic Name

English

GANCICLOVIR [MART.]

Common Name

English

VITRASERT

Brand Name

English

ZIRGAN

Brand Name

English

GANCICLOVIR [ORANGE BOOK]

Common Name

English

RS-21592

Code

English

BW-759U

Code

English

ganciclovir [INN]

Common Name

English

GANCICLOVIR [EP MONOGRAPH]

Common Name

English

GANCICLOVIR [VANDF]

Common Name

English

NSC-759656

Code

English

GANCICLOVIR [MI]

Common Name

English

GANCICLOVIR [USP-RS]

Common Name

English

GANCICLOVIR [JAN]

Common Name

English

GANCYCLOVIR

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

237607