VIDARABINE ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H13N5O4
Molecular Weight	267.2413
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC=NC2=C1N=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3O

InChI

InChIKey=OIRDTQYFTABQOQ-UHTZMRCNSA-N

InChI=1S/C10H13N5O4/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10/h2-4,6-7,10,16-18H,1H2,(H2,11,12,13)/t4-,6-,7+,10-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019937s024lbl.pdfhttps://www.drugbank.ca/drugs/DB00194

Vidarabine or 9-β-D-arabinofuranosyladenine (ara-A, trade name Vira-A) is a synthetic purine nucleoside analog with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of Vidarabine is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts Vidarabine into Vidarabine monophosphate, a nucleotide analog. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. in vitro, Vidarabine triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, Vidarabine triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where Vidarabine 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenosine receptor 34 Target ID: CHEMBL2111329 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17438146	Agonist 2662
Human herpesvirus 1 DNA polymerase 17 Target ID: CHEMBL1872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24047739	Inhibitor 8228
Thymidine kinase 16 Target ID: CHEMBL1075062 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17438061	Substrate 656

Conditions

Condition	Modality	Highest Phase	Product
Paroxysmal supraventricular tachycardia 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019937s024lbl.pdf	Primary	Approved 8360	ADENOCARD Approved Use Intravenous Adenocard (adenosine injection) is indicated for the following. Conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver), should be attempted prior to Adenocard administration. Launch Date 6.2570883E11
Keratoconjunctivitis 7 Sources: https://www.drugs.com/pro/vira-a.html	Curative	Approved 8360	VIRA-A Approved Use Unknown Launch Date 2.17814401E11
Epithelial keratitis 5 Sources: https://www.drugs.com/pro/vira-a.html	Curative	Approved 8360	VIRA-A Approved Use Unknown Launch Date 2.17814401E11
Herpes simplex infection 27 Sources: https://clinicaltrials.gov/ct2/show/NCT00000985	Primary	Phase III 663	VIRA-A Approved Use Unknown Launch Date 2.17814401E11

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1348236	7.5 mg/kg 1 times / day multiple, intravenous dose: 7.5 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		HYPOXANTHINE ARABINOSIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 595

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/21103968/	yes

PubMed

Title	Date	PubMed
Anti-herpesvirus activity of adenine arabinoside analogues in tissue culture and a genital infection of mice and guinea pigs.	1982 May	6179469
Effect of combinations of acyclovir with vidarabine or its 5'-monophosphate on herpes simplex viruses in cell culture and in mice.	1982 Sep	6182836
Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis.	1999 Sep-Oct	10533957
Adenine-induced selective apoptosis toward HIV chronically infected cells in vitro.	2000 Jul 14	10891366
Metabolic fate of extracellular NAD in human skin fibroblasts.	2001	11135366
Effects of postsynaptic GABA(B) receptor activation on epileptiform activity in hippocampal slices.	2001	11077079
Adenosine A(1) and A(3) receptors mediate inhibition of synaptic transmission in rat cortical neurons.	2001	11077074
Autoimmune thrombocytopenia associated with the first cycle of fludarabine therapy in the treatment of relapsed non-Hodgkin's lymphoma.	2001	11554624
Treatment of aggressive, or progressing indolent peripheral T- and NK-cell neoplasias by combination of fludarabine, cyclophosphamide and doxorubicine.	2001 Apr	11441297
Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients.	2001 Aug	11489799
Impact of therapy With chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup Study Cancer and Leukemia Group B 9011.	2001 Aug 15	11504743
Glucocorticoids protect against apoptosis induced by serum deprivation, cyclic adenosine 3',5'-monophosphate and p53 activation in immortalized human granulosa cells: involvement of Bcl-2.	2001 Feb	11159853
The effects of P2Y receptor agonists and adenosine on prostaglandin production by the guinea-pig uterus.	2001 Feb	11159724
Mechanism of prolonged vasorelaxation to ATP in the rat isolated mesenteric arterial bed.	2001 Feb	11159721
Elevated interstitial adenosine concentrations do not activate the muscle reflex.	2001 Feb	11158950
Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells.	2001 Feb	11158054
Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.	2001 Feb	11156949
Molecular remission following high-dose hydroxyurea and fludarabine plus cytarabine in a patient with simultaneous acute myeloid leukemia and low-grade lymphoma.	2001 Feb	11426540
Second primary tumors and immune phenomena after fludarabine or 2-chloro-2'-deoxyadenosine treatment.	2001 Feb	11426527
Deoxynucleoside kinases encoded by the yaaG and yaaF genes of Bacillus subtilis. Substrate specificity and kinetic analysis of deoxyguanosine kinase with UTP as the preferred phosphate donor.	2001 Feb 23	11078735
The main products of the low molecular mass fraction in the venom of the spider Latrodectus menavodi.	2001 Feb-Mar	10978765
Effects of extracellular nucleotides and nucleosides on prostate carcinoma cells.	2001 Jan	11159704
The critical role of adenosine and guanosine in the affinity of dinucleoside polyphosphates to P(2X)-receptors in the isolated perfused rat kidney.	2001 Jan	11159696
Two subtypes of G protein-coupled nucleotide receptors, P2Y(1) and P2Y(2) are involved in calcium signalling in glioma C6 cells.	2001 Jan	11159687
Activity of adenosine diphosphates and triphosphates on a P2Y(T) -type receptor in brain capillary endothelial cells.	2001 Jan	11156575
Quantitative assessment of myocardial perfusion during graded coronary stenosis by real-time myocardial contrast echo refilling curves.	2001 Jan	11153750
Purines inhibit poly(ADP-ribose) polymerase activation and modulate oxidant-induced cell death.	2001 Jan	11149897
Efferent arteriole tubuloglomerular feedback in the renal nephron.	2001 Jan	11135074
Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells.	2001 Jan	11125033
S-Adenosyl-L-homocysteine hydrolase inhibitor mediates immunosuppressive effects in vivo: suppression of delayed type hypersensitivity ear swelling and peptidoglycan polysaccharide-induced arthritis.	2001 Jan	11123369
Short-term hibernation in adult cardiomyocytes is PO(2) dependent and Ca(2+) mediated.	2001 Jan	11123216
Preconditioning of the distal portion of a rat random-pattern skin flap.	2001 Jan	11121320
Interleukin-6 enhances expression of adenosine A(1) receptor mRNA and signaling in cultured rat cortical astrocytes and brain slices.	2001 Jan	11106879
Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia.	2001 Jan 1	11123332
Vasoactive intestinal peptide-stimulated adenosine 3',5'-cyclic monophosphate formation in cerebral cortex and hypothalamus of chick and rat: comparison of the chicken and mammalian peptide.	2001 Jan 12	11121878
Repeated administration of CGP 46381, a gamma-aminobutyric acidB antagonist, and ethosuximide suppresses seizure-associated cyclic adenosine 3'5' monophosphate response element- and activator protein-1 DNA-binding activities in lethargic (lh/lh) mice.	2001 Jan 19	11137764
Nucleotide-dependent single- to double-headed binding of kinesin.	2001 Jan 26	11158681
Nucleoside transport inhibition in ischemic myocardium results in enhanced taurine efflux.	2001 Jan 5	11137869
Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation.	2001 Jul	11509933
Flavopiridol circumvents Bcl-2 family mediated inhibition of apoptosis and drug resistance in B-cell chronic lymphocytic leukaemia.	2001 Jul	11472347
Imbalanced DNA synthesis induced by cytosine arabinoside and fludarabine in human leukemia cells.	2001 Jul 1	11377401
Will mixed chimerism cure autoimmune diseases after a nonmyeloablative stem cell transplant?	2001 Jul 27	11477365
Nucleoside analogues in the treatment of haematological malignancies.	2001 Jun	11585009
Efficacy of fludarabine, intermittent sequential high-dose cytosine arabinoside, and mitoxantrone (FIS-HAM) salvage therapy in highly resistant acute leukemias.	2001 Jun	11475146
Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect.	2001 Jun	11458521
ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999.	2001 Mar 16	11104774
Cytosolic high K(m) 5'-nucleotidase and 5'(3')-deoxyribonucleotidase in substrate cycles involved in nucleotide metabolism.	2001 Mar 2	11083867
Equilibrium binding of single-stranded DNA to the secondary DNA binding site of the bacterial recombinase RecA.	2001 Mar 30	11121401
Phosphodiesterase type 4 inhibitor suppresses expression of anti-apoptotic members of the Bcl-2 family in B-CLL cells and induces caspase-dependent apoptosis.	2001 Oct	11587214
Cyclosporin A for the treatment of cytopenia associated with chronic lymphocytic leukemia.	2001 Oct 15	11596014

Patents

Sample Use Guides

In Vivo Use Guide

Adult Patients: Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1-2 second period). Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1-2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required. Pediatric Patients: Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow. Repeat administration: If conversion of PSVT does not occur within 1-2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. Pediatric Patients with a Body Weight ≥ 50 kg: Administer the adult dose.

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Name

Type

Language

VIDARABINE ANHYDROUS

Common Name

English

NSC-404241

Code

English

NSC-247519

Code

English

ARASENA-A

Brand Name

English

VIDARABINE [HSDB]

Common Name

English

9-.BETA.-D-ARABINOFURANOSYL-9H-PURIN-6-AMINE

Common Name

English

VIDARABINE [MI]

Common Name

English

VIDARABINE, ANHYDROUS

Common Name

English

vidarabine [INN]

Common Name

English

9H-PURIN-6-AMINE, 9-.BETA.-D-ARABINOFURANOSYL-

Common Name

English

CI-673

Code

English

VIRA-A

Brand Name

English

Vidarabine [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J05AB03