Repositioning Candidate Details

Candidate ID: R0364
Source ID: DB01004
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Ganciclovir
Synonyms: 2-(6-Amino-purin-9-ylmethoxy)-propane-1,3-diol; 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-1H-purin-6(9H)-one; 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-3H-purin-6(9H)-one; 2-amino-9-((1,3-dihydroxypropan-2-yloxy)methyl)-9H-purin-6-ol; 2-Amino-9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-1,9-dihydro-purin-6-one; 2-amino-9-(2-hydroxy-1-hydroxymethylethoxymethyl)-6,9-dihydro-1H-6-purinone; 9-((2-Hydroxy-1-(hydroxymethyl)ethoxy)methyl)guanine; 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine; GA2; Ganciclovir; Gancyclovir
Molecular Formula: C9H13N5O4
SMILES: NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1
Structure:
DrugBank Description: An acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections.
CAS Number: 82410-32-0
Molecular Weight: 255.2306
DrugBank Indication: For induction and maintenance in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Also used in the treatment of severe cytomegalovirus (CMV) disease, including CMV pneumonia, CMV gastrointestinal disease, and disseminated CMV infections, in immunocompromised patients.
DrugBank Pharmacology: Ganciclovir is a synthetic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses both <i>in vitro</i> and <i>in vivo</i>. Sensitive human viruses include cytomegalovirus (CMV), herpes simplex virus -1 and -2 (HSV-1, HSV-2), Epstein-Barr virus (EBV) and varicella zoster virus (VZV), however clinical studies have been limited to assessment of efficacy in patients with CMV infection. Ganciclovir is a prodrug that is structurally similar to acyclovir. It inhibits virus replication by its encorporation into viral DNA. This encorporation inhibits dATP and leads to defective DNA, ceasing or retarding the viral machinery required to spread the virus to other cells.
DrugBank MoA: Ganciclovir's antiviral activity inhibits virus replication. This inhibitory action is highly selective as the drug must be converted to the active form by a virus-encoded cellular enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellular guanylate kinase and into the triphosphate by a number of cellular enzymes. <i>In vitro</i>, ganciclovir triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, ganciclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ganciclovir 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. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.
Targets: DNA polymerase catalytic subunit inhibitor; DNA incorporation into and destabilization; Thymidine kinase inducer
Inclusion Criteria: Indication associated