Details
Stereochemistry | ACHIRAL |
Molecular Formula | C9H12N5O4.Na |
Molecular Weight | 277.2124 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].NC1=NC2=C(N=CN2COC(CO)CO)C(=O)[N-]1
InChI
InChIKey=JJICLMJFIKGAAU-UHFFFAOYSA-M
InChI=1S/C9H13N5O4.Na/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);/q;+1/p-1
DescriptionSources: 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.pdfCurator'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
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.
Originator
Sources: https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=19960131&CC=EP&NR=0694547A2&KC=A2http://shodhganga.inflibnet.ac.in/bitstream/10603/2450/15/15_chapter%204.pdf
Curator's Comment: The first synthesis of ganciclovir was reported by Julien Verheyden and John Martin at Syntex Research in California in 1980 and is marketed as sodium salt (Ganciclovir sodium) under the trade names Cytovene and Cymevene.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P08546 Gene ID: NA Gene Symbol: UL54 Target Organism: Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) |
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Target ID: CHEMBL3414 |
0.08 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ZIRGAN Approved UseZIRGAN is a topical ophthalmic antiviral that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). Launch Date1995 |
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Primary | CYTOVENE Approved UseCYTOVENE-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 Date1994 |
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Primary | VALCYTE Approved UseVALCYTE is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Launch Date2001 |
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Primary | VALCYTE Approved UseVALCYTE is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk Launch Date2001 |
Cmax
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 |
T1/2
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: |
unhealthy, 37.4 n = 19 Health Status: unhealthy Condition: AIDS Age Group: 37.4 Population Size: 19 Sources: |
|
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: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Other AEs: Neutropenia, Thrombocytopenia... Other AEs: Neutropenia (18%) Sources: Thrombocytopenia (4%) Anemia (severe, 4%) Renal impairment (4%) |
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: |
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: |
Other AEs: Neutropenia... |
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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Other AEs: Fever, Infection... Other AEs: Fever (48%) Sources: 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%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Neutropenia | 18% | 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: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Renal impairment | 4% | 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: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Thrombocytopenia | 4% | 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: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Anemia | severe, 4% | 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: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Neutropenia | 22% | 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: |
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: |
Chills | 10% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Sweating | 12% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Infection | 13% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Vomiting | 13% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Anorexia | 14% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Sepsis | 15% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Anemia | 25% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Leukopenia | 41% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Diarrhea | 44% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Fever | 48% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Pruritus | 5% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Thrombocytopenia | 6% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Catheter sepsis | 8% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Catheter infection | 9% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Neuropathy | 9% | 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: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/22777050/ |
PubMed
Title | Date | PubMed |
---|---|---|
Design and SAR study of a novel class of nucleotide analogues as potent anti-HCMV agents. | 1999 Apr-May |
|
Ganciclovir-induced encephalopathy in a bone marrow transplant recipient. | 1999 Aug |
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Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs. | 1999 Dec |
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Phenotypic and genetic characterization of thymidine kinase from clinical strains of varicella-zoster virus resistant to acyclovir. | 1999 Oct |
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Human cytomegalovirus: challenges, opportunities and new drug development. | 1999 Sep |
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The cyclohexene ring system as a furanose mimic: synthesis and antiviral activity of both enantiomers of cyclohexenylguanine. | 2000 Feb 24 |
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Synthesis and antiviral evaluation of halogenated beta-D- and -L-erythrofuranosylbenzimidazoles. | 2000 Jun 15 |
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Thienothiadiazine 2,2-dioxide acyclonucleosides: synthesis and antiviral activity. | 2000 May |
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Synthesis and enantioselectivity of the antiviral effects of (R,Z)-,(S,Z)-methylenecyclopropane analogues of purine nucleosides and phosphoralaninate prodrugs: influence of heterocyclic base, type of virus and host cells. | 2000 May |
|
Indolocarbazoles exhibit strong antiviral activity against human cytomegalovirus and are potent inhibitors of the pUL97 protein kinase. | 2000 Oct |
|
Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. | 2000 Oct |
|
Prophylaxis against herpesvirus infections in transplant recipients. | 2001 |
|
Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector. | 2001 Apr |
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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 |
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A time to live, a time to die. | 2001 Apr 15 |
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Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase controlled by thyroglobulin promoter demonstrates high specificity and low toxicity. | 2001 Feb |
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[Cytomegalovirus rhombencephalomyelitis in an immunocompetent subject]. | 2001 Feb |
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Immune-dependent distant bystander effect after adenovirus-mediated suicide gene transfer in a rat model of liver colorectal metastasis. | 2001 Feb |
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A tightly regulated immortalized human fetal hepatocyte cell line to develop a bioartificial liver. | 2001 Feb-Mar |
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Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir? | 2001 Feb-Mar |
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Preemptive ganciclovir for CMV viremia in liver transplantation. | 2001 Feb-Mar |
|
Prophylactic antiviral therapy in CMV high-risk liver transplant recipients. | 2001 Feb-Mar |
|
Is preemptive therapy for CMV infection following liver transplantation superior to symptom-triggered treatment? | 2001 Feb-Mar |
|
Cytomegalovirus infection-enhanced chronic rejection in the rat is prevented by antiviral prophylaxis. | 2001 Feb-Mar |
|
Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment. | 2001 Jan |
|
Recurrent disseminated herpes zoster and cytomegalic perianal ulcer: a case report and review of the literature. | 2001 Jan |
|
Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and. | 2001 Jan |
|
[Gene therapy for colorectal cancer]. | 2001 Jan |
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[Perspectives on postgenome medicine: Gene therapy for brain tumors]. | 2001 Jan |
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In vitro effects of antiviral agents on human keratocytes. | 2001 Jan |
|
Management of complications associated with totally implantable ports in patients with AIDS. | 2001 Jan |
|
Cytomegalovirus hemorrhagic gastritis. | 2001 Jan |
|
Isolation and analysis of an aciclovir-resistant murine cytomegalovirus mutant. | 2001 Jan |
|
Ganciclovir-loaded albumin nanoparticles: characterization and in vitro release properties. | 2001 Jan |
|
Molecular mechanism for ganciclovir resistance in human T lymphocytes transduced with retroviral vectors carrying the herpes simplex virus thymidine kinase gene. | 2001 Jan 1 |
|
Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation. | 2001 Jan 15 |
|
Mutations conferring ganciclovir resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis. | 2001 Jan 15 |
|
Human beta-herpesvirus interactions in solid organ transplant recipients. | 2001 Jan 15 |
|
Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient. | 2001 Mar |
|
Characterization of the cyclooxygenase-2 promoter in an adenoviral vector and its application for the mitigation of toxicity in suicide gene therapy of gastrointestinal cancers. | 2001 Mar |
|
New developments in the management of cytomegalovirus infection and disease after renal transplantation. | 2001 Mar |
|
Protease pretreatment increases the efficacy of adenovirus-mediated gene therapy for the treatment of an experimental glioblastoma model. | 2001 Mar 1 |
|
Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells. | 2001 Mar 1 |
|
Preemptive therapy versus universal prophylaxis with ganciclovir for cytomegalovirus in solid organ transplant recipients. | 2001 Mar 1 |
|
Prophylaxis for CMV should not now replace pre-emptive therapy in solid organ transplantation. | 2001 Mar-Apr |
|
Reactivity of valganciclovir in aqueous solution. | 2005 Oct |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1556
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NCI_THESAURUS |
C29575
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NCI_THESAURUS |
C281
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FDA ORPHAN DRUG |
7985
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Code System | Code | Type | Description | ||
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SUB02312MIG
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Ganciclovir sodium
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DTXSID20883175
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82131
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Z-46
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CHEMBL182
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DBSALT000309
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02L083W284
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23700083
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100000089399
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107910-75-8
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02L083W284
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C1588
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m5663
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PRIMARY | Merck Index |
ACTIVE MOIETY
SUBSTANCE RECORD