DIDOX

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 Search

SMILES

ONC(=O)C1=CC(O)=C(O)C=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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28624910
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 integrase 19 Target ID: CHEMBL3471 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9083483	Inhibitor 8297
Ribonucleotide reductase 8 Target ID: CHEMBL3301398 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28624910	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28624910	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

Title	Date	PubMed
Selective inhibition of l kappaB alpha phosphorylation and HIV-1 LTR-directed gene expression by novel antioxidant compounds.	1997 Aug 4	9268159
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	10606163
Activation of caspases and induction of apoptosis by novel ribonucleotide reductase inhibitors amidox and didox.	2001 May	11376876
Suppression of retrovirus-induced immunodeficiency disease (murine AIDS) by trimidox and didox: novel ribonucleotide reductase inhibitors with less bone marrow toxicity than hydroxyurea.	2002 Nov	12367722
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 Jan 15	12504799
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 Aug	15133626
Combination chemotherapy of BCNU and Didox acts synergystically in 9L glioma cells.	2004 Oct	15571292
Inhibition of ribonucleotide reductase reduces neointimal formation following balloon injury.	2005 Jul	15814568
Ribonucleotide reductase inhibitors enhance cidofovir-induced apoptosis in EBV-positive nasopharyngeal carcinoma xenografts.	2005 Sep 10	15818619
Didox, a ribonucleotide reductase inhibitor, induces apoptosis and inhibits DNA repair in multiple myeloma cells.	2006 Oct	16925573
Ribonucleotide reductase inhibitors hydroxyurea, didox, and trimidox inhibit human cytomegalovirus replication in vitro and synergize with ganciclovir.	2013 Oct	23933116
3,4-Dihydroxy-benzohydroxamic acid (Didox) suppresses pro-inflammatory profiles and oxidative stress in TLR4-activated RAW264.7 murine macrophages.	2015 May 25	25843059

Patents

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 `Fri Dec 15 19:05:08 GMT 2023` Edited by `admin` on `Fri Dec 15 19:05:08 GMT 2023`
Record UNII	L106XFV0RQ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DIDOX

Common Name

English

NSC-324360

Code

English

N-3,4-TRIDHYDROXY-BENZAMIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2150