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Details

Stereochemistry RACEMIC
Molecular Formula C7H12N2S2
Molecular Weight 188.314
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PX-12

SMILES

CCC(C)SSC1=NC=CN1

InChI

InChIKey=BPBPYQWMFCTCNG-UHFFFAOYSA-N
InChI=1S/C7H12N2S2/c1-3-6(2)10-11-7-8-4-5-9-7/h4-6H,3H2,1-2H3,(H,8,9)

HIDE SMILES / InChI

Molecular Formula C7H12N2S2
Molecular Weight 188.314
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00417287 | https://www.ncbi.nlm.nih.gov/pubmed/23327656 | https://clinicaltrials.gov/ct2/show/NCT00736372 | https://www.ncbi.nlm.nih.gov/pubmed/24172913

DB05448 (PX-12, 1-methyl propyl 2-imidazolyl disulfide) is a small molecule irreversible inhibitor of the redox protein thioredoxin, which has been associated with cancer and tumor growth. DB05448 stimulates apoptosis, down-regulates HIF-1α and vascular endothelial growth factor (VEGF) and inhibits tumor growth in animal models. Since high levels of Trx-1 have been associated with colorectal, gastric and lung cancers, DB05448 is indicated as a potential cancer treatment in combination with chemotherapy for patients with advanced metastatic cancer. Initial trials correlated doses of DB05448 with increased patient survival.

Originator

Sources: European Journal of Medicinal Chemistry (1992), 27, (1), 33-7

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.11 µM [IC50]
Target ID: Q16881|||Q6VB41|||Q6YNQ1
Gene ID: 7296.0
Gene Symbol: TXNRD1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 37.2212 uM]
yes
PubMed

PubMed

TitleDatePubMed
Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication.
2001 Oct 1
Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women.
2003 Jul
Patents

Patents

Sample Use Guides

3 hour intravenous infusion as a dose of either 54 mg/m2 or 128 mg/m2 daily for 5 days every three weeks.
Route of Administration: Intravenous
Human lung cancer Calu-6 cells were used for activity evaluation. 1×10^4 cells per well were seeded in 96-well microtiter plates (Nunc). After incubation with the 1, 2, 3, 4 and 5 mkM of PX-12 (DB05448) for the 72 h, MTT solution [20 μl; 2 mg/ml in phosphate-buffered saline (PBS)] was added to each well of the 96-well plates. The plates were additionally incubated for 3 h at 37 °C. Medium was removed from the plates by pipetting, and 200 μl DMSO was added to each well to solubilize the formazan crystals. The optical density was measured at 570 nm using a microplate reader (Synergy™ 2, BioTek Instruments Inc., Winooski, VT, USA).
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:48:26 UTC 2023
Edited
by admin
on Fri Dec 15 15:48:26 UTC 2023
Record UNII
8PQ9CZ8BTJ
Record Status Validated (UNII)
Record Version
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Name Type Language
PX-12
Common Name English
1-METHYLPROPYL-2-IMIDAZOLYL DISULFIDE
Systematic Name English
Code System Code Type Description
NCI_THESAURUS
C74082
Created by admin on Fri Dec 15 15:48:26 UTC 2023 , Edited by admin on Fri Dec 15 15:48:26 UTC 2023
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PUBCHEM
219104
Created by admin on Fri Dec 15 15:48:26 UTC 2023 , Edited by admin on Fri Dec 15 15:48:26 UTC 2023
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DRUG BANK
DB05448
Created by admin on Fri Dec 15 15:48:26 UTC 2023 , Edited by admin on Fri Dec 15 15:48:26 UTC 2023
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CAS
141400-58-0
Created by admin on Fri Dec 15 15:48:26 UTC 2023 , Edited by admin on Fri Dec 15 15:48:26 UTC 2023
PRIMARY
FDA UNII
8PQ9CZ8BTJ
Created by admin on Fri Dec 15 15:48:26 UTC 2023 , Edited by admin on Fri Dec 15 15:48:26 UTC 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY