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: 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
Allogeneic cell therapy for patients who relapse after autologous stem cell transplantation.	2001	11349810
Successful salvage of RAEB/AML relapsing early post allograft with FLAG-Ida conditioned mini-allograft: a report of two cases.	2001 Apr	11488854
Double reinforcement with fludarabine/high-dose cytarabine enhances the impact of autologous stem cell transplantation in acute myeloid leukemia patients.	2001 Apr	11477440
Fludarabine for chronic lymphocytic leukemia.	2001 Apr 12	11302143
Evaluation of the combination of nelarabine and fludarabine in leukemias: clinical response, pharmacokinetics, and pharmacodynamics in leukemia cells.	2001 Apr 15	11304766
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
Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen.	2001 Aug	11535991
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
Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients.	2001 Aug	11489799
Erythroleukaemia in the north of England: a population based study.	2001 Aug	11477115
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
First line therapy with fludarabine combinations in 42 patients with either post myelodysplastic syndrome or therapy related acute myeloid leukaemia.	2001 Jan	11426552
Treatment of "poor risk" acute myeloid leukemia with fludarabine, cytarabine and G-CSF (flag regimen): a single center study.	2001 Jan	11426551
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
Lethal adenovirus infection in a patient who had undergone nonmyeloablative stem cell transplantation.	2001 Jul	11530814
Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation.	2001 Jul	11509933
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
Flavopiridol circumvents Bcl-2 family mediated inhibition of apoptosis and drug resistance in B-cell chronic lymphocytic leukaemia.	2001 Jul	11472347
Evaluating treatment strategies in chronic lymphocytic leukemia: use of quality-adjusted survival analysis.	2001 Jul	11438417
Will mixed chimerism cure autoimmune diseases after a nonmyeloablative stem cell transplant?	2001 Jul 27	11477365
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
Cost of de novo acute myeloid leukemia induction therapy in adults: analysis of EORTC-GIMEMA AML10 and FLANG regimens.	2001 Jun	11484970
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
[Chronic lymphatic leukemia. 3. The concrete case].	2001 Jun 8	11464816
[Chronic lymphocytic leukemia. 2. Therapy].	2001 Jun 8	11441667
Vidarabine therapy for severe chronic active Epstein-Barr virus infection.	2001 Jun-Jul	11464986
Reversal of fludarabine induced testicular damage in a patient with chronic lymphocytic leukaemia (CLL), by suppression of pituitary-testicular axis using gonadotrophin releasing hormone (GnRH).	2001 Mar	11342377
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
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
Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation.	2001 May 1	11303263
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
Non-myeloablative conditioning regimen of fludarabine, busulfan, anti-thymocyte globulin, and methylprednisolone for allogeneic peripheral blood hematopoietic cell transplantation.	2001 Sep	11532635
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.

Name

Type

Language

VIDARABINE PHOSPHATE

Official Name

English

VIDARABINE PHOSPHATE [MART.]

Common Name

English

NSC-127223

Code

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