VIDARABINE PHOSPHATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H14N5O7P
Molecular Weight	347.2212
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](COP(O)(O)=O)[C@@H](O)[C@@H]3O

InChI

InChIKey=UDMBCSSLTHHNCD-UHTZMRCNSA-N

InChI=1S/C10H14N5O7P/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(22-10)1-21-23(18,19)20/h2-4,6-7,10,16-17H,1H2,(H2,11,12,13)(H2,18,19,20)/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 35 Target ID: CHEMBL2111329 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17438146	Agonist 2752
Human herpesvirus 1 DNA polymerase 24 Target ID: CHEMBL1872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24047739	Inhibitor 8504
Thymidine kinase 17 Target ID: CHEMBL1075062 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17438061	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Paroxysmal supraventricular tachycardia 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019937s024lbl.pdf	Primary	Approved 8583	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 1989
Keratoconjunctivitis 7 Sources: https://www.drugs.com/pro/vira-a.html	Curative	Approved 8583	VIRA-A Approved Use Unknown Launch Date 1976
Epithelial keratitis 5 Sources: https://www.drugs.com/pro/vira-a.html	Curative	Approved 8583	VIRA-A Approved Use Unknown Launch Date 1976
Herpes simplex infection 28 Sources: https://clinicaltrials.gov/ct2/show/NCT00000985	Primary	Phase III 665	VIRA-A Approved Use Unknown Launch Date 1976

C_max

Value	Dose	Analyte	Population
0.17 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359193/	2.5 mg single, intravenous dose: 2.5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.48 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359193/	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.78 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359193/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
10 s DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/fecdce1e-4233-f44c-e053-6294a90a714f/spl-doc?hl=adenosine	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.92 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359193/	2.5 mg single, intravenous dose: 2.5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.24 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359193/	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.86 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359193/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.63 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8359193/	0.6 μg/kg single, intravenous dose: 0.6 μg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
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

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.017% EXPERIMENT https://pubs.acs.org/doi/epdf/10.1021/acs.jmedchem.6b00866	0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ADENOSINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 725

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21103968/	yes

PubMed

Title	Date	PubMed
Distinct modulation of evoked and spontaneous EPSCs by purinoceptors in the nucleus tractus solitarii of the rat.	2001-02-01	11158277
Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency.	2001-02-01	11157502
Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.	2001-02-01	11157478
Adenosine-mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum.	2001-02-01	11157094
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.	2001-02	11159853
The effects of P2Y receptor agonists and adenosine on prostaglandin production by the guinea-pig uterus.	2001-02	11159724
Mechanism of prolonged vasorelaxation to ATP in the rat isolated mesenteric arterial bed.	2001-02	11159721
Regulation of G protein-coupled receptor-adenylyl cyclase responsiveness in human airway smooth muscle by exogenous and autocrine adenosine.	2001-02	11159049
Protein tyrosine phosphatase-dependent proteolysis of focal adhesion complexes in endothelial cell apoptosis.	2001-02	11159014
K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation.	2001-02	11158988
Regional differences in mechanisms of cerebral circulatory response to neuronal activation.	2001-02	11158982
Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion.	2001-02	11158956
Elevated interstitial adenosine concentrations do not activate the muscle reflex.	2001-02	11158950
New signaling pathways for hormones and cyclic adenosine 3',5'-monophosphate action in endocrine cells.	2001-02	11158328
Beta,gamma-methylene ATP-induced cAMP formation in C6Bu-1 cells: involvement of local metabolism and subsequent stimulation of adenosine A2B receptor.	2001-02	11158259
Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection.	2001-02	11158213
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.	2001-02	11158054
Adenosine triphosphate-evoked cytosolic calcium oscillations in human granulosa-luteal cells: role of protein kinase C.	2001-02	11158045
Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.	2001-02	11156949
Dysregulation of extracellular adenosine levels by vascular smooth muscle cells from spontaneously hypertensive rats.	2001-02	11156861
Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors.	2001-02	11137880
Nucleotide-dependent single- to double-headed binding of kinesin.	2001-01-26	11158681
Estrogen modulates norepinephrine-induced accumulation of adenosine cyclic monophosphate in a subpopulation of immortalized luteinizing hormone-releasing hormone secreting neurons from the mouse hypothalamus.	2001-01-26	11154836
Differential patterns of sympathetic responses to selective stimulation of nucleus tractus solitarius purinergic receptor subtypes.	2001-01-12	11153527
Structure-activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors.	2001-01-08	11140740
Expression, but not activity, of neuronal nitric oxide synthase is regionally increased in the alcoholic brain.	2001-01-05	11139418
Nucleoside transport inhibition in ischemic myocardium results in enhanced taurine efflux.	2001-01-05	11137869
Motivational effects of ethanol in DARPP-32 knock-out mice.	2001-01-01	11150351
Effects of extracellular nucleotides and nucleosides on prostate carcinoma cells.	2001-01	11159704
The critical role of adenosine and guanosine in the affinity of dinucleoside polyphosphates to P(2X)-receptors in the isolated perfused rat kidney.	2001-01	11159696
Two subtypes of G protein-coupled nucleotide receptors, P2Y(1) and P2Y(2) are involved in calcium signalling in glioma C6 cells.	2001-01	11159687
Nitrogen-dependent accumulation of cytokinins in root and the translocation to leaf: implication of cytokinin species that induces gene expression of maize response regulator.	2001-01	11158447
Activity of adenosine diphosphates and triphosphates on a P2Y(T) -type receptor in brain capillary endothelial cells.	2001-01	11156575
Potentiation of cytokine induction of group IIA phospholipase A(2) in rat mesangial cells by ATP and adenosine via the A2A adenosine receptor.	2001-01	11156559
Quantitative relationship between the chemical structure of antisense nucleosides and their capacity to interact with cyclomalto-octaose.	2001-01	11154902
Sildenafil citrate (Viagra) does not exacerbate myocardial ischemia in canine models of coronary artery stenosis.	2001-01	11153753
Quantitative assessment of myocardial perfusion during graded coronary stenosis by real-time myocardial contrast echo refilling curves.	2001-01	11153750
Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries.	2001-01	11153726
Hoechst 33342-induced apoptosis is associated with intracellular accumulation of E2F-1 protein in BC3H-1 myocytes and HL-60 cells.	2001-01	11151061
Extracellular ATP formation on vascular endothelial cells is mediated by ecto-nucleotide kinase activities via phosphotransfer reactions.	2001-01	11149913
Purines inhibit poly(ADP-ribose) polymerase activation and modulate oxidant-induced cell death.	2001-01	11149897
Differential effect of adenosine on tumor and normal cell growth: focus on the A3 adenosine receptor.	2001-01	11147810
Paroxysmal supraventricular tachycardia: outcome after ED care.	2001-01	11146016
A novel transverse push-pull microprobe: in vitro characterization and in vivo demonstration of the enzymatic production of adenosine in the spinal cord dorsal horn.	2001-01	11145997
Cellular distribution of constitutively active mutant parathyroid hormone (PTH)/PTH-related protein receptors and regulation of cyclic adenosine 3',5'-monophosphate signaling by beta-arrestin2.	2001-01	11145746
Effects of neuroprotective cocktails on hippocampal neuron death in an in vitro model of cerebral ischemia.	2001-01	11145473
Pharmacokinetic-pharmacodynamic modeling of the antilipolytic effects of an adenosine receptor agonist in healthy volunteers.	2001-01	11144995
Influence of adduct position and sequence length on the ligation of oligonucleotides containing benzo[c]phenanthrene diol epoxide-deoxyadenosine adducts into M13mp7L2.	2001-01	11139600
P2 receptor agonists stimulate insulin release from human pancreatic islets.	2001-01	11138974
Regulation of platelet aggregation in vitro by plasma adenosine in preeclampsia.	2001	11150873

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

NSC-127223

Preferred Name

English

VIDARABINE PHOSPHATE

Official Name

English

VIDARABINE PHOSPHATE [MART.]

Common Name

English

9-.BETA.-D-ARABINOFURANOSYLADENINE 5'-(DIHYDROGEN PHOSPHATE)

Common Name

English

VIDARABINE PHOSPHATE [USAN]

Common Name

English

9H-PURIN-6-AMINE, 9-(5-O-PHOSPHONO-.BETA.-D-ARABINOFURANOSYL)-

Common Name

English

CL-808

Code

English

Vidarabine phosphate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29575