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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H13FN2O4
Molecular Weight 244.2196
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALOVUDINE

SMILES

CC1=CN([C@H]2C[C@H](F)[C@@H](CO)O2)C(=O)NC1=O

InChI

InChIKey=UXCAQJAQSWSNPQ-XLPZGREQSA-N
InChI=1S/C10H13FN2O4/c1-5-3-13(10(16)12-9(5)15)8-2-6(11)7(4-14)17-8/h3,6-8,14H,2,4H2,1H3,(H,12,15,16)/t6-,7+,8+/m0/s1

HIDE SMILES / InChI

Molecular Formula C10H13FN2O4
Molecular Weight 244.2196
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02232581 | https://www.ncbi.nlm.nih.gov/pubmed/17461857 | https://clinicaltrials.gov/ct2/show/NCT00002271 | https://www.ncbi.nlm.nih.gov/pubmed/17628710

Alovudine (3’ -deoxy-3’ fluorothymidine) is a nucleoside reverse transcriptase inhibitor (NRTI) initially tested in the early 1990s, before the era of combination therapy and before the availability of plasma viral load measurement. Initial toxicity studies showed that the primary target organ of toxicity was the bone marrow. A lack of clear advantages in activity over zidovudine, the only drug approved in the early 1990s, and the potential for bone marrow toxicity caused alovudine development to be stopped [6]. However, later in vitro studies found alovudine to be very effective at suppressing several NRTI-resistant HIV-1 mutants, including isolates with multiple thymidine-associated mutations (TAMs) or multi-NRTI-resistance mutations. Alovudine at a dose of 7.5 mg/day added to a failing antiretroviral combined regimen in patients with isolates resistant to other NRTIs yielded a median viral load decline after a 4-week period in patients not receiving concomitant stavudine. In July 2003, Medivir out-licensed it's HIV antiviral MIV-310 to Boehringer Ingelheim. Under the terms of the agreement, Boehringer Ingelheim will make upfront and milestone payments to Medivir totaling up to 122 million euro in the event that all development and performance milestones are met. In March 2005, Boehringer Ingelheim recently completed a clinical trial of MIV-310 (alovudine) in HIV/AIDS. The efficacy exhibited by MIV-310 at the doses tested showed antiviral activity but did not achieve the target level of efficacy which had previously been defined. Boehringer Ingelheim, therefore, decided to stop the development of this investigational drug.

Originator

Sources: Acta Biologica et Medica Germanica (1969), 23, (6), 759-66.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer












Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
3',3'-Difluoro-3'-deoxythymidine: comparison of anti-HIV activity to 3'-fluoro-3'-deoxythymidine.
1992 Sep 4
In vitro anti-hepatitis B virus activities of 5"-O-myristoyl analogue derivatives of 3"-fluoro-2",3"-dideoxythymidine (FLT) and 3"-azido-2",3"-dideoxythymidine (AZT).
1998 Sep-Dec
Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells.
2002 Sep
Correspondence re: H. Barthel et al., 3'-deoxy-3'-[(18)F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res., 63: 3791-3798, 2003.
2003 Dec 1
Alovudine Medivir.
2003 Feb
Potential impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer.
2003 Jul
3'-deoxy-3'-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography.
2003 Jul 1
3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) as positron emission tomography tracer for imaging proliferation in a murine B-Cell lymphoma model and in the human disease.
2003 May 15
PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls.
2003 Sep
Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.
2003 Sep 15
MIV-310 reduces HIV viral load in patients failing multiple antiretroviral therapy: results from a 4-week phase II study.
2004 Jun 18
Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation.
2004 Mar
PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study.
2004 May
New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections.
2004 Oct
[Fluorinated analogs of nucleosides and fluorinated tracers of gene expression for positron emission tomography].
2004 Sep
Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides.
2005 Dec 15
Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3'-deoxy-3'-18F-fluorothymidine PET.
2005 Jan
Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.
2005 Mar
A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and retention.
2005 Nov
[Is 3'-deoxy-3'- [18F] fluorothymidine ([18F]-FLT) the next tracer for routine clinical PET after R [18F]-FDG?].
2005 Sep
Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models.
2006 Aug 1
In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography.
2006 Aug 1
Functional imaging for early prediction of response to chemoradiotherapy: 3'-deoxy-3'-18F-fluorothymidine positron emission tomography--a clinical application model of esophageal cancer.
2006 Dec
Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.
2006 Dec
18F-fluorothymidine kinetics of malignant brain tumors.
2007 Jul
Patents

Patents

Sample Use Guides

0.5, 1 and 2 mg for 4 weeks
Route of Administration: Oral
HepG2 cells were used for activity evaluation. HepG2 cells were cultured in six-well plates at an initial concentration of 2 × 106 cells per well, and exposed to the test compounds (Alovudine) at concentrations of 0.3, 1, 3, 10, 30, 100 and 300mkM in duplicate; 0.1% DMSO and culture were used as controls. The cells were incubated at 37 ◦C under 5% CO2. The culture medium consisted of Minimal Essential Medium (MEM: Invitrogen-Gibco, Paisley, United Kingdom) supplemented with 10% fetal bovine serum albumin, sodium pyruvate (1 mM), 100,000g/ml streptomycin sulphate (Invitrogen-Gibco) and 100,000 U/ml penicillin G. The adherent cells were washed with phosphate-buffered saline (PBS) before being split by trypsinization with 1×trypsin solution (Invitrogen-Gibco) every third day. After counting the number of cells in the samples, 3 × 105 cells were taken for analysis of mitochondrial DNA. These cells were dispensed into lysis buffer (bioMerieux, Boxtel, The Netherlands) and stored at −80 ◦C prior to analysis. During counting the relative number of dead cells that remained in the culture after washing was determined by Trypan blue exclusion. The absolute number of dead cells in the adherent culture could not be determined, as the cells would have had to be trypsinized before counting, in turn necessitating thorough washing of the cells with PBS to eliminate residual proteins, which would have removed the dead cells.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:25:34 GMT 2023
Edited
by admin
on Sat Dec 16 17:25:34 GMT 2023
Record UNII
PG53R0DWDQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALOVUDINE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
ALOVUDINE [USAN]
Common Name English
CL-184824
Code English
CL-184,824
Code English
3'-DEOXY-3'-FLUOROTHYMIDINE
Systematic Name English
CL 184824
Code English
NSC-140025
Code English
FLUOROTHYMIDINE
Systematic Name English
alovudine [INN]
Common Name English
Alovudine [WHO-DD]
Common Name English
CL 184,824
Code English
Classification Tree Code System Code
NCI_THESAURUS C97452
Created by admin on Sat Dec 16 17:25:34 GMT 2023 , Edited by admin on Sat Dec 16 17:25:34 GMT 2023
Code System Code Type Description
EVMPD
SUB05359MIG
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PRIMARY
DRUG BANK
DB06198
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PRIMARY
MESH
C002854
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PRIMARY
ChEMBL
CHEMBL105318
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PRIMARY
EPA CompTox
DTXSID4046579
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PRIMARY
FDA UNII
PG53R0DWDQ
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PRIMARY
USAN
EE-7
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PRIMARY
INN
6992
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PRIMARY
PUBCHEM
33039
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PRIMARY
WIKIPEDIA
ALOVUDINE
Created by admin on Sat Dec 16 17:25:34 GMT 2023 , Edited by admin on Sat Dec 16 17:25:34 GMT 2023
PRIMARY
NCI_THESAURUS
C65226
Created by admin on Sat Dec 16 17:25:34 GMT 2023 , Edited by admin on Sat Dec 16 17:25:34 GMT 2023
PRIMARY
EVMPD
SUB33340
Created by admin on Sat Dec 16 17:25:34 GMT 2023 , Edited by admin on Sat Dec 16 17:25:34 GMT 2023
ALTERNATIVE
NSC
140025
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PRIMARY
SMS_ID
100000087447
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PRIMARY
CAS
25526-93-6
Created by admin on Sat Dec 16 17:25:34 GMT 2023 , Edited by admin on Sat Dec 16 17:25:34 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY