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	H2O
Molecular Weight	18.0153
Charge	0
Count

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

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

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 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

Effect of 9-beta-D-arabinofuranosyladenine 5'-monophosphate and 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate on experimental herpes simplex keratitis.	1976 Dec	1008546
[Preliminary clinical experiences with adenine arabinoside monophosphate (ARA-AMP) in encephalitis due to viruses of the herpes group and varicella/zoster infections (author's transl)].	1979 Nov	92592
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
Comparison of the antiviral effects of 5-methoxymethyldeoxyuridine-5'-monophosphate with adenine arabinoside-5'-monophosphate.	1983 Sep	6197027
Inhibitory effects of 2'-fluorinated arabinosyl-pyrimidine nucleosides on woodchuck hepatitis virus replication in chronically infected woodchucks.	1990 Mar	2334160
Liver targeting of nucleoside analogues coupled to galactosyl terminating macromolecules: a new approach to the treatment of a chronic viral hepatitis.	1997 Jun	9646223
Autoimmune thrombocytopenia associated with the first cycle of fludarabine therapy in the treatment of relapsed non-Hodgkin's lymphoma.	2001	11554624
Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma with fludarabine.	2001	11408715
Successful salvage of RAEB/AML relapsing early post allograft with FLAG-Ida conditioned mini-allograft: a report of two cases.	2001 Apr	11488854
[Mantle cell lymphoma].	2001 Apr	11400298
Fludarabine and cytarabine as a sequential infusion regimen for treatment of adults with recurrent, refractory or poor prognosis acute leukemia.	2001 Apr	11378544
Fludarabine for chronic lymphocytic leukemia.	2001 Apr 12	11302142
Fludarabine for chronic lymphocytic leukemia.	2001 Apr 12	11302140
[Molecular biology examination in chronic lymphocytic leukemia].	2001 Apr 22	11340945
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
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
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
Fludarabine, arabinosyl cytosine and idarubicin (FLAI) for remission induction in poor-risk acute myeloid leukemia.	2001 Jan	11426555
First line therapy with fludarabine combinations in 42 patients with either post myelodysplastic syndrome or therapy related acute myeloid leukaemia.	2001 Jan	11426552
Second allogeneic peripheral blood stem cell transplantation with fludarabine-based low-intensity conditioning regimen for relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation.	2001 Jan	11372748
Unrelated cord blood transplantation in a Fanconi anemia patient using fludarabine-based conditioning.	2001 Jul	11498756
Acute left ventricular failure following melphalan and fludarabine conditioning.	2001 Jul	11498753
Successful HLA-identical bone marrow transplantation in a patient with PNP deficiency using busulfan and fludarabine for conditioning.	2001 Jul	11498751
Evaluating treatment strategies in chronic lymphocytic leukemia: use of quality-adjusted survival analysis.	2001 Jul	11438417
Herpes simplex virus dermatitis in patients using latanoprost.	2001 Jul	11438068
Imbalanced DNA synthesis induced by cytosine arabinoside and fludarabine in human leukemia cells.	2001 Jul 1	11377401
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
Combination chemotherapy and rituximab.	2001 Jun	11508932
Non-myeloablative hematopoietic stem cell transplantation.	2001 Jun	11499966
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
[Chronic lymphocytic leukemia. 2. Therapy].	2001 Jun 8	11441667
Fludarabine in alkylator-resistant follicular non-Hodgkin's lymphoma.	2001 Mar	11342365
Early allogeneic blood stem cell transplantation after modified conditioning therapy during marrow aplasia: stable remission in high-risk acute myeloid leukemia.	2001 Mar	11313690
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
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
Cathepsins are upregulated by IFN-gamma/STAT1 in human muscle culture: a possible active factor in dermatomyositis.	2001 Sep	11556541
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 `Thu Jul 06 10:57:32 UTC 2023` Edited by `admin` on `Thu Jul 06 10:57:32 UTC 2023`
Record UNII	FA2DM6879K
Record Status	`Validated (UNII)`
Record Version

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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