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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

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
In vitro screening for antiretroviral agents against simian immunodeficiency virus (SIV).
1990 Aug
Long-term tolerance and efficacy of 3'-azidothymidine and 3'-fluorothymidine treatment of asymptomatic monkeys infected with simian immunodeficiency virus.
1992 Aug
Use of a standardized cell culture assay to assess activities of nucleoside analogs against hepatitis B virus replication.
1992 Jul 1
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
Anti-HIV type 1 activity of 3'-fluoro-3'-deoxythymidine for several different multidrug-resistant mutants.
2001 Mar 20
Rat studies comparing 11C-FMAU, 18F-FLT, and 76Br-BFU as proliferation markers.
2002 Dec
A new precursor for the radiosynthesis of [18F]FLT.
2002 Feb
Synthesis, solution conformation and anti-HIV activity of novel 3'-substituted-2',3'-dideoxy-5-hydroxymethyluridines and their 4,5-substituted analogues.
2003 May
Thiated analogues of 2',3'-dideoxy-3'-fluorothymidine and their phosphorylated and phosphonylated derivatives: synthesis, interaction with HIV reverse transcriptase, and in vitro anti-HIV activity.
2003 May-Aug
Effect of probenecid and quinidine on the transport of alovudine (3'-fluorothymidine) to the rat brain studied by microdialysis.
2003 Nov
[18F]FLT PET for diagnosis and staging of thoracic tumours.
2003 Oct
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
[18F]FLT-PET in oncology: current status and opportunities.
2004 Dec
Evaluation of 3'-deoxy-3'-18F-fluorothymidine for monitoring tumor response to radiotherapy and photodynamic therapy in mice.
2004 Oct
Molecular imaging in animal models of disease--every little detail counts!
2005 Aug
18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors.
2005 Dec
Kinetic analysis of 3'-deoxy-3'-fluorothymidine PET studies: validation studies in patients with lung cancer.
2005 Feb
Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3'-deoxy-3'-18F-fluorothymidine PET.
2005 Jan
The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels.
2005 Mar
Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.
2005 Mar
Reproducibility of 3'-deoxy-3'-(18)F-fluorothymidine microPET studies in tumor xenografts in mice.
2005 Nov
A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and retention.
2005 Nov
Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033.
2006 Apr
Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.
2006 Dec
Acquisition of resistance to antitumor alkylating agent ACNU: a possible target of positron emission tomography monitoring.
2006 Jan
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.
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
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PRIMARY
NCI_THESAURUS
C65226
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PRIMARY
EVMPD
SUB33340
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ALTERNATIVE
NSC
140025
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PRIMARY
SMS_ID
100000087447
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PRIMARY
CAS
25526-93-6
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PRIMARY