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Details

Stereochemistry ACHIRAL
Molecular Formula C7H7NO4
Molecular Weight 169.1348
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIDOX

SMILES

ONC(=O)C1=CC=C(O)C(O)=C1

InChI

InChIKey=QJMCKEPOKRERLN-UHFFFAOYSA-N
InChI=1S/C7H7NO4/c9-5-2-1-4(3-6(5)10)7(11)8-12/h1-3,9-10,12H,(H,8,11)

HIDE SMILES / InChI
Molecular Formula C7H7NO4
Molecular Weight 169.1348
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28964543 | https://www.ncbi.nlm.nih.gov/pubmed/28750923 | https://www.ncbi.nlm.nih.gov/pubmed/1764386

Didox is a simple, synthetic antioxidant and a ribonucleotide reductase inhibitor with activity against retroviruses. Didox inhibits retrovirus replication by depleting the deoxynucleotides obligatory for the synthesis of the proviral DNA intermediate of retrovirus replication. It also increases the radiosensitivity of cancer cells by inhibition of ribonucleotide reductase, resulting in a reduction of BCL-2 mediated resistance to apoptosis. Didox has been found to reduce the levels of oxidative injury markers in the brains of HIV patients with dementia. Didox has been evaluated in various phase I and phase II trials but Didox did not demonstrate any efficacy response in patients.

Originator

Carlsson, I.A.|Lindqvist, M.|Fila-Hromadko, S.|Corrodi, H.
1
Sources: Helvetica Chimica Acta (1962), 45, 270-6.

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
Inhibitor
8504
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.7 μg/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25698442
265 mg/m² single, intravenous
dose: 265 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIDOX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
8 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25698442
265 mg/m² single, intravenous
dose: 265 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIDOX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.8 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25698442
265 mg/m² single, intravenous
dose: 265 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIDOX plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
3,4-Dihydroxy-benzohydroxamic acid (Didox) suppresses pro-inflammatory profiles and oxidative stress in TLR4-activated RAW264.7 murine macrophages.
2015-05-25
Ribonucleotide reductase inhibitors hydroxyurea, didox, and trimidox inhibit human cytomegalovirus replication in vitro and synergize with ganciclovir.
2013-10
Ribonucleotide reductase inhibitors reduce atherosclerosis in a double-injury rabbit model.
2009-12
Didox, a ribonucleotide reductase inhibitor, induces apoptosis and inhibits DNA repair in multiple myeloma cells.
2006-10
Robust vascular protective effect of hydroxamic acid derivatives in a sickle mouse model of inflammation.
2006-09
Ribonucleotide reductase inhibitors enhance cidofovir-induced apoptosis in EBV-positive nasopharyngeal carcinoma xenografts.
2005-09-10
Inhibition of ribonucleotide reductase reduces neointimal formation following balloon injury.
2005-07
Combination of inhibitors of lymphocyte activation (hydroxyurea, trimidox, and didox) and reverse transcriptase (didanosine) suppresses development of murine retrovirus-induced lymphoproliferative disease.
2005-01
Combination chemotherapy of BCNU and Didox acts synergystically in 9L glioma cells.
2004-10
Synergistic cytotoxicity of the ribonucleotide reductase inhibitor didox (3,4-dihydroxy-benzohydroxamic acid) and the alkylating agent carmustine (BCNU) in 9L rat gliosarcoma cells and DAOY human medulloblastoma cells.
2004-08
In vivo examination of hydroxyurea and the novel ribonucleotide reductase inhibitors trimidox and didox in combination with the reverse transcriptase inhibitor abacavir: suppression of retrovirus-induced immunodeficiency disease.
2004-06
Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance.
2003-01-15
Didox (a novel ribonucleotide reductase inhibitor) overcomes Bcl-2 mediated radiation resistance in prostate cancer cell line PC-3.
2002-12-24
Suppression of retrovirus-induced immunodeficiency disease (murine AIDS) by trimidox and didox: novel ribonucleotide reductase inhibitors with less bone marrow toxicity than hydroxyurea.
2002-11
Short-term treatment with novel ribonucleotide reductase inhibitors Trimidox and Didox reverses late-stage murine retrovirus-induced lymphoproliferative disease with less bone marrow toxicity than hydroxyurea.
2002-09
Activation of caspases and induction of apoptosis by novel ribonucleotide reductase inhibitors amidox and didox.
2001-05
In vivo and in vitro comparison of the short-term hematopoietic toxicity between hydroxyurea and trimidox or didox, novel ribonucleotide reductase inhibitors with potential anti-HIV-1 activity.
1999
Selective inhibition of l kappaB alpha phosphorylation and HIV-1 LTR-directed gene expression by novel antioxidant compounds.
1997-08-04
Depsides and depsidones as inhibitors of HIV-1 integrase: discovery of novel inhibitors through 3D database searching.
1997-03-14
Patents

Patents

WO2017165218
2

Sample Use Guides

In Vivo Use Guide
6 g/m^2 given by intravenous infusion over 36 h every 3 weeks.
Route of Administration: Intravenous
In Vitro Use Guide
Mast cells were sensitized overnight with 0.5 mg/mL anti-DNP mouse IgE (k isotype). Next, cells were washed and resusupended at 1×10^6 cells/mL with IL-3 and SCF (10 ng/mL). Crosslinking (XL) was induced by the addition of DNP-HSA (50 ng/mL) for 18 h. Didox (10-200mkM) or vehicle control (DEPC water) was added for 6 h prior to IgE activation.
Substance Class Chemical
Created
by admin
on Mon Mar 31 19:31:52 GMT 2025
Edited
by admin
on Mon Mar 31 19:31:52 GMT 2025
Record UNII
L106XFV0RQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NSC-324360
Preferred Name English
DIDOX
Common Name English
N-3,4-TRIDHYDROXY-BENZAMIDE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2150
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
NCI_THESAURUS C1660
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
Code System Code Type Description
MESH
C035419
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
NCI_THESAURUS
C1338
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
DRUG BANK
DB12948
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
NSC
324360
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
PUBCHEM
3045
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
CAS
69839-83-4
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
FDA UNII
L106XFV0RQ
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
EPA CompTox
DTXSID90220134
Created by admin on Mon Mar 31 19:31:52 GMT 2025 , Edited by admin on Mon Mar 31 19:31:52 GMT 2025
PRIMARY
NIH
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