title: Vidarabine is neither a potent nor a selective AC5 inhibitor.
abstract: Vidarabine was the first clinically approved antiviral drug, but due to safety and efficacy issues the drug is currently only used topically for herpes virus keratitis. Scientific interest in vidarabine has been recently renewed due to the fact that the compound exhibits beneficial effects in animal models of heart failure and cancer, replicating effects of the knockout of adenylyl cyclase 5 (AC5). Therefore, vidarabine has been suggested to mediate these effects via selective inhibition of AC5. Based on these results, clinical studies with vidarabine in humans for heart failure and cancer have been proposed. Here, evidence is presented that vidarabine is neither a potent nor a selective AC5 inhibitor. Greatest caution should be exerted when proposing new mechanisms of actions and clinical uses for vidarabine.
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: seifert.roland@mh-hannover.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D014740:Vidarabine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000998:Antiviral Agents; D007527:Isoenzymes; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V; D014740:Vidarabine
keywords: Adenylyl cyclase 5; Cancer; Heart failure; P-site inhibitor; Vidarabine