VIDARABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H13N5O4.H2O
Molecular Weight	285.2566
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=ZTHWFVSEMLMLKT-CAMOTBBTSA-N

InChI=1S/C10H13N5O4.H2O/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);1H2/t4-,6-,7+,10-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C10H13N5O4
Molecular Weight	267.2413
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB00194http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019937s024lbl.pdf

Adenosine is a nucleoside that is composed of adenine and d-ribose, occurring in all cells of the body and play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Adenocard (adenosine injection) is used as an initial treatment for the termination of paroxysmal supraventricular tachycardia (PVST), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). When clinically advisable, appropriate vagal maneuvers. Adenocard does not convert atrial flutter, atrial fibrillation, or ventricular tachycardia to normal sinus rhythm. In the presence of atrial flutter or atrial fibrillation, a transient modest slowing of ventricular response may occur immediately following Adenocard administration. Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the A-V node, and can restore normal sinus rhythm. This effect may be mediated through the drug's activation of cell-surface A1 and A2 adenosine receptors. Adenocard is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenocard is not blocked by atropine. Adenosine also inhibits the slow inward calcium current and activation of adenylate cyclase in smooth muscle cells, thereby causing relaxation of vascular smooth muscle. By increasing blood flow in normal coronary arteries with little or no increase in stenotic arteries, adenosine produces a relative difference in thallous (thallium) chloride TI 201 uptake in myocardium supplied by normal verus stenotic coronary arteries.

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 2678
Human herpesvirus 1 DNA polymerase 19 Target ID: CHEMBL1872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24047739	Inhibitor 8297
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 8429	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 8429	VIRA-A Approved Use Unknown Launch Date 1976
Epithelial keratitis 5 Sources: https://www.drugs.com/pro/vira-a.html	Curative	Approved 8429	VIRA-A Approved Use Unknown Launch Date 1976
Herpes simplex infection 28 Sources: https://clinicaltrials.gov/ct2/show/NCT00000985	Primary	Phase III 656	VIRA-A Approved Use Unknown Launch Date 1976

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 599

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21103968/	yes

PubMed

Title	Date	PubMed
Autoimmune thrombocytopenia associated with the first cycle of fludarabine therapy in the treatment of relapsed non-Hodgkin's lymphoma.	2001	11554624
A systematic overview of chemotherapy effects in B-cell chronic lymphocytic leukaemia.	2001	11441934
Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma with fludarabine.	2001	11408715
Double reinforcement with fludarabine/high-dose cytarabine enhances the impact of autologous stem cell transplantation in acute myeloid leukemia patients.	2001 Apr	11477440
Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections.	2001 Apr	11292644
Recombinant bacterial cells as efficient biocatalysts for the production of nucleosides.	2001 Apr-Jul	11563158
Mito-flag as salvage therapy for relapsed and refractory acute myeloid leukemia.	2001 Aug	11574763
Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study Group.	2001 Aug	11529853
Erythroleukaemia in the north of England: a population based study.	2001 Aug	11477115
Reactivation of hepatitis B virus infection during cytotoxic chemotherapy.	2001 Feb	11232724
A case of refractory idiopathic pure red cell aplasia responsive to fludarabine treatment.	2001 Feb	11167858
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
Regional differences in mechanisms of cerebral circulatory response to neuronal activation.	2001 Feb	11158982
Adenosine triphosphate-evoked cytosolic calcium oscillations in human granulosa-luteal cells: role of protein kinase C.	2001 Feb	11158045
Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.	2001 Feb	11156949
Dysregulation of extracellular adenosine levels by vascular smooth muscle cells from spontaneously hypertensive rats.	2001 Feb	11156861
Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.	2001 Feb 1	11157478
Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency.	2001 Feb 1	11157502
Adenosine-mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum.	2001 Feb 1	11157094
A fludarabine-based conditioning regimen for severe aplastic anemia.	2001 Jan	11281379
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
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 Jan	11158447
Extracellular ATP formation on vascular endothelial cells is mediated by ecto-nucleotide kinase activities via phosphotransfer reactions.	2001 Jan	11149913
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 Jan	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 Jan	11145746
Nucleotide-dependent single- to double-headed binding of kinesin.	2001 Jan 26	11158681
Structure-activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors.	2001 Jan 8	11140740
Evaluating treatment strategies in chronic lymphocytic leukemia: use of quality-adjusted survival analysis.	2001 Jul	11438417
Treatment options in Waldenström's macroglobulinaemia: the role of the purine analogues.	2001 Jun	11585010
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
Nucleoside analogues: mechanisms of drug resistance and reversal strategies.	2001 Jun	11417472
UCN-01 induces cytotoxicity toward human CLL cells through a p53-independent mechanism.	2001 Jun	11378265
Indolent aspergillus arthritis complicating fludarabine-based non-myeloablative stem cell transplantation.	2001 Mar	11319599
Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation.	2001 Mar	11274765
New drug combinations for the treatment of murine AIDS and macrophage protection.	2001 Mar	11264653
Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia.	2001 Mar 1	11230486
Retrospective study of the prognostic role of serum thymidine kinase level in CLL patients with active disease treated with fludarabine.	2001 May	11432619
A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma.	2001 May	11359390
Fludarabine pharmacokinetics after subcutaneous and intravenous administration in patients with lupus nephritis.	2001 May	11349741
Novel treatment strategies in chronic lymphocytic leukemia.	2001 May	11296131
Early full donor myeloid chimerism after reduced-intensity stem cell transplantation using a combination of fludarabine and busulfan.	2001 Oct	11602413
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
High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens.	2001 Oct 15	11596013
Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone.	2001 Sep	11564066
Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis.	2001 Sep	11516109
Therapeutic options for acute myelogenous leukemia.	2001 Sep 1	11571716

Patents

Sample Use Guides

In Vivo Use Guide

Administer approximately one-half inch of Vira-A Ophthalmic Ointment (Vidarabine), 3%, into the lower conjunctival sac five times daily at three-hour intervals.

Route of Administration: Topical

In Vitro Use Guide

Confluent monolayers of Vero cells in 12-well microplates were infected with approximately 200 PFU of virus and incubated at 37°C with twofold serial dilutions of antiviral drug. After 1 h, the inoculum was removed and replaced with medium containing 1% methylcellulose and Vidarabine. Control wells did not contain antiviral drugs. The cells were fixed in 100% methanol 40 h after infection and were stained with Giemsa stain. Plaques were visually inspected and counted using a dissecting microscope. The number of plaques at each drug concentration was plotted versus the log of the drug concentration, and the slope of the regression line in the linear range was determined. The amount of Vidarabine required to reduce the number of plaques by 50% from those in the control wells (EC50) was calculated from the equation of the regression line. Vidarabine was tested against each isolate at least twice in replicate wells, and the EC50 was calculated as an average value. Cytotoxicity in Vero cells for all the compounds was determined previously using a 3-(4,5- dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:10:21 GMT 2023` Edited by `admin` on `Sat Dec 16 05:10:21 GMT 2023`
Record UNII	FA2DM6879K
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

VIDARABINE

Official Name

English

VIDARABINE [JAN]

Common Name

English

VIDARABINE [USAN]

Common Name

English

9-.BETA.-D-ARABINOFURANOSYLADENINE MONOHYDRATE

Systematic Name

English

VIDARABINE [MART.]

Common Name

English

VIDARABINE MONOHYDRATE

Common Name

English

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

Systematic Name

English

NSC-757383

Code

English

ARA-A

Code

English

VIDARABINE [USP IMPURITY]

Common Name

English

VIDARABINE [VANDF]

Common Name

English

VIDARABINE MONOHYDRATE [MI]

Common Name

English

VIDARABINE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QS01AD06