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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
Comparison of in vitro biological properties and mouse toxicities of three thymidine analogs active against human immunodeficiency virus.
1990 Apr
In vitro screening for antiretroviral agents against simian immunodeficiency virus (SIV).
1990 Aug
Synergistic inhibition of human immunodeficiency virus replication in vitro by combinations of 3'-azido-3'-deoxythymidine and 3'-fluoro-3'-deoxythymidine.
1990 Oct
5'-O-phosphonomethyl-2',3'-dideoxynucleosides: synthesis and anti-HIV activity.
1990 Sep
Advances in positron emission tomographic imaging of lung cancer.
2005
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
Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides.
2005 Dec 15
Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies.
2005 Feb
Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.
2005 Jun
[18F]3'-deoxy-3'-fluorothymidine PET for the diagnosis and grading of brain tumors.
2005 Jun
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
In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase.
2005 Mar
Antiadenovirus activities of several classes of nucleoside and nucleotide analogues.
2005 Mar
Emerging anti-HIV drugs.
2005 May
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 May 15
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
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 Nov 1
Molecular imaging: what can be used today.
2005 Nov 23
True tracers: comparing FDG with glucose and FLT with thymidine.
2005 Oct
[Is 3'-deoxy-3'- [18F] fluorothymidine ([18F]-FLT) the next tracer for routine clinical PET after R [18F]-FDG?].
2005 Sep
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
Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033.
2006 Apr
Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors.
2006 Apr
Clinical molecular imaging with positron emission tomography.
2006 Aug
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
[Correlation of 3'-deoxy-3'-18F-fluorothymidine uptake to cell proliferation in lung carcinoma xenografts].
2006 Dec
Fluorine-18 fluorothymidine: a new positron emission radioisotope for renal tumors.
2006 Dec
Evaluation of primary brain tumors with FLT-PET: usefulness and limitations.
2006 Dec
Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-fluorodeoxyglucose-positron emission tomography.
2006 Feb
Positron emission tomography in patients with breast cancer using (18)F-3'-deoxy-3'-fluoro-l-thymidine ((18)F-FLT)-a pilot study.
2006 Feb
Semiautomatic synthesis of 3'-deoxy-3'-[18F]fluorothymidine using three precursors.
2006 Feb
3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods.
2006 Feb 15
Acquisition of resistance to antitumor alkylating agent ACNU: a possible target of positron emission tomography monitoring.
2006 Jan
Is 3'-deoxy-3'-(18)F-fluorothymidine a better marker for tumour response than (18)F-fluorodeoxyglucose?
2006 Jul
Molecular imaging of proliferation in malignant lymphoma.
2006 Nov 15
Kinetic analysis of 3'-deoxy-3'-18F-fluorothymidine in patients with gliomas.
2006 Oct
18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment.
2006 Oct
[PET and malignant cerebral tumors].
2006 Sep
Quantifying the activity of adenoviral E1A CR2 deletion mutants using renilla luciferase bioluminescence and 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography imaging.
2006 Sep 15
Impact of integrated PET/CT on variability of target volume delineation in rectal cancer.
2007 Feb
Imaging-guided gene therapy of experimental gliomas.
2007 Feb 15
18F-fluorothymidine kinetics of malignant brain tumors.
2007 Jul
PET imaging with [18F]3'-deoxy-3'-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer.
2007 Jun
Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel.
2007 Mar
18F-fluorodeoxythymidine PET for evaluating the response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcomas.
2007 Mar
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 UTC 2023
Edited
by admin
on Sat Dec 16 17:25:34 UTC 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 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
Code System Code Type Description
EVMPD
SUB05359MIG
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
DRUG BANK
DB06198
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
MESH
C002854
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
ChEMBL
CHEMBL105318
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
EPA CompTox
DTXSID4046579
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
FDA UNII
PG53R0DWDQ
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
USAN
EE-7
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
INN
6992
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
PUBCHEM
33039
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
WIKIPEDIA
ALOVUDINE
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
NCI_THESAURUS
C65226
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
EVMPD
SUB33340
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
ALTERNATIVE
NSC
140025
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
SMS_ID
100000087447
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
CAS
25526-93-6
Created by admin on Sat Dec 16 17:25:34 UTC 2023 , Edited by admin on Sat Dec 16 17:25:34 UTC 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY