DB00194 - Vidarabine
| Identification | |
|---|---|
| Name | Vidarabine |
| Accession Number | DB00194 (APRD00333, EXPT02753) |
| Type | small molecule |
| Description | A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia VIRUS and varicella zoster virus. [PubChem] |
| Structure |
|
| Categories (*) | |
| Molecular Weight | 267.2413 |
| Groups | approved |
| Monoisotopic Weight | 267.096753929 |
| Pharmacology | |
| Indication | For treatment of chickenpox - varicella, herpes zoster and herpes simplex |
| Mechanism of action | Vidarabine stops replication of herpes viral DNA in 2 ways: 1) competitive inhibition of viral DNA polymerase, and consequently 2) incorporation into and termination of the growing viral DNA chain. This drug is a nucleoside analog and therefore has to be phosphorylated to be active. Vidarabine is sequentially phosphorylated by kinases to the triphosphate ara-ATP. This is the active form of vidarabine and is both an inhibitor and a substrate of viral DNA polymerase. When used as a substrate for viral DNA polymerase, ara-ATP competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ara-ATP 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 |
| Absorption | Systemetic absorption of vidarabine should not be expected to occur following ocular administration and swallowing lacrimal secretions. |
| Protein binding | 24-38% |
| Biotransformation | In laboratory animals, vidarabine is rapidly deaminated in the gastrointestinal tract to Ara-Hx. |
| Route of elimination | Not Available |
| Toxicity | Acute massive overdosage by oral ingestion of the ophthalmic ointment has not occurred. However, the rapid deamination to arabinosylhypoxanthine should preclude any difficulty. The oral LD50 for vidarabine is greater than 5020 mg/kg in mice and rats. No untoward effects should result from ingestion of the entire contents of the tube. Overdosage by ocular instillation is unlikely because any excess should be quickly expelled from the conjunctival sac. |
| Affected organisms |
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| Interactions | |
| Drug Interactions | Not Available |
| Food Interactions | Not Available |
Targets
| DNA polymerase | |
|---|---|
| Name | DNA polymerase |
| Gene Name | BALF5 |
| Pharmacological action | yes |
| Actions | inhibitor |
| References |
|
| DTHybrid score | 0.0464 |
| DNA | |
| Name | DNA |
| Gene Name | Not Available |
| Pharmacological action | yes |
| Actions | incorporation into and destabilization |
| References | |
| DTHybrid score | Not Available |
| Thymidine kinase | |
| Name | Thymidine kinase |
| Gene Name | ORF36 |
| Pharmacological action | yes |
| Actions | inducer |
| References |
|
| DTHybrid score | 1.2461 |
| Thymidine kinase | |
| Name | Thymidine kinase |
| Gene Name | TK |
| Pharmacological action | yes |
| Actions | inducer |
| References |
|
| DTHybrid score | 1.2461 |
Enzymes
| Adenosine deaminase | |
|---|---|
| Name | Adenosine deaminase |
| Gene Name | ADA |
| Actions | substrate |
| References |
|
| DTHybrid score | 1.6421 |