U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 victim

Drug as victim

Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
18F-fluorothymidine kinetics of malignant brain tumors.
2007-07
PET imaging with [18F]3'-deoxy-3'-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer.
2007-06
Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel.
2007-03
18F-fluorodeoxythymidine PET for evaluating the response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcomas.
2007-03
Imaging-guided gene therapy of experimental gliomas.
2007-02-15
Impact of integrated PET/CT on variability of target volume delineation in rectal cancer.
2007-02
Functional imaging for early prediction of response to chemoradiotherapy: 3'-deoxy-3'-18F-fluorothymidine positron emission tomography--a clinical application model of esophageal cancer.
2006-12
[Correlation of 3'-deoxy-3'-18F-fluorothymidine uptake to cell proliferation in lung carcinoma xenografts].
2006-12
Fluorine-18 fluorothymidine: a new positron emission radioisotope for renal tumors.
2006-12
Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.
2006-12
Molecular imaging of proliferation in malignant lymphoma.
2006-11-15
Kinetic analysis of 3'-deoxy-3'-18F-fluorothymidine in patients with gliomas.
2006-10
18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment.
2006-10
Quantifying the activity of adenoviral E1A CR2 deletion mutants using renilla luciferase bioluminescence and 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography imaging.
2006-09-15
[PET and malignant cerebral tumors].
2006-09
Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models.
2006-08-01
In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography.
2006-08-01
Clinical molecular imaging with positron emission tomography.
2006-08
Is 3'-deoxy-3'-(18)F-fluorothymidine a better marker for tumour response than (18)F-fluorodeoxyglucose?
2006-07
Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033.
2006-04
Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors.
2006-04
3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods.
2006-02-15
Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-fluorodeoxyglucose-positron emission tomography.
2006-02
Positron emission tomography in patients with breast cancer using (18)F-3'-deoxy-3'-fluoro-l-thymidine ((18)F-FLT)-a pilot study.
2006-02
Semiautomatic synthesis of 3'-deoxy-3'-[18F]fluorothymidine using three precursors.
2006-02
Acquisition of resistance to antitumor alkylating agent ACNU: a possible target of positron emission tomography monitoring.
2006-01
The effect of a methyl or 2-fluoroethyl substituent at the N-3 position of thymidine, 3'-fluoro-3'-deoxythymidine and 1-beta-D-arabinosylthymine on their antiviral and cytostatic activity in cell culture.
2006
Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides.
2005-12-15
18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors.
2005-12
Molecular imaging: what can be used today.
2005-11-23
Quantification of cellular proliferation in tumor and normal tissues of patients with breast cancer by [18F]fluorothymidine-positron emission tomography imaging: evaluation of analytical methods.
2005-11-01
Reproducibility of 3'-deoxy-3'-(18)F-fluorothymidine microPET studies in tumor xenografts in mice.
2005-11
A simplified analysis of [18F]3'-deoxy-3'-fluorothymidine metabolism and retention.
2005-11
True tracers: comparing FDG with glucose and FLT with thymidine.
2005-10
[Is 3'-deoxy-3'- [18F] fluorothymidine ([18F]-FLT) the next tracer for routine clinical PET after R [18F]-FDG?].
2005-09
Molecular imaging in animal models of disease--every little detail counts!
2005-08
Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.
2005-06
[18F]3'-deoxy-3'-fluorothymidine PET for the diagnosis and grading of brain tumors.
2005-06
Early detection of tumor response to chemotherapy by 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo.
2005-05-15
Emerging anti-HIV drugs.
2005-05
The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels.
2005-03
Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.
2005-03
In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase.
2005-03
Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.
2005-03
Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies.
2005-02
Advances in positron emission tomographic imaging of lung cancer.
2005
Synergistic inhibition of human immunodeficiency virus replication in vitro by combinations of 3'-azido-3'-deoxythymidine and 3'-fluoro-3'-deoxythymidine.
1990-10
5'-O-phosphonomethyl-2',3'-dideoxynucleosides: synthesis and anti-HIV activity.
1990-09
In vitro screening for antiretroviral agents against simian immunodeficiency virus (SIV).
1990-08
Comparison of in vitro biological properties and mouse toxicities of three thymidine analogs active against human immunodeficiency virus.
1990-04
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 Wed Apr 02 09:06:15 GMT 2025
Edited
by admin
on Wed Apr 02 09:06:15 GMT 2025
Record UNII
PG53R0DWDQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALOVUDINE
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
CL 184,824
Preferred 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
MIV310
Code English
NSC-140025
Code English
FLUOROTHYMIDINE
Systematic Name English
alovudine [INN]
Common Name English
MIV-310
Code English
Alovudine [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C97452
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
Code System Code Type Description
EVMPD
SUB05359MIG
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
DRUG BANK
DB06198
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
MESH
C002854
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
ChEMBL
CHEMBL105318
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
EPA CompTox
DTXSID4046579
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
FDA UNII
PG53R0DWDQ
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
USAN
EE-7
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
INN
6992
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
PUBCHEM
33039
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
WIKIPEDIA
ALOVUDINE
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
NCI_THESAURUS
C65226
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
EVMPD
SUB33340
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
ALTERNATIVE
NSC
140025
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
SMS_ID
100000087447
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
CAS
25526-93-6
Created by admin on Wed Apr 02 09:06:15 GMT 2025 , Edited by admin on Wed Apr 02 09:06:15 GMT 2025
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY