PX-12

Investigational

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 Search

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
Sources: https://www.drugbank.ca/drugs/DB05448
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thioredoxin 2 Target ID: CHEMBL2010624 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23327656	Inhibitor 8504		2.11 µM [IC50]
Thioredoxin reductase 1, cytoplasmic 3 Target ID: Q16881\|\|\|Q6VB41\|\|\|Q6YNQ1 Gene ID: 7296.0 Gene Symbol: TXNRD1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12657718 \| https://www.ncbi.nlm.nih.gov/pubmed/9605422	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pancreatic cancer 98 Sources: https://clinicaltrials.gov/ct2/show/NCT00417287	Primary		Phase II 1147	Unknown Approved Use Unknown
Metastatic cancer 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00736372	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
12 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	36 mg/m² single, intravenous dose: 36 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
29.01 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	72 mg/m² single, intravenous dose: 72 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
30 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	54 mg/m² single, intravenous dose: 54 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
20 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	72 mg/m² single, intravenous dose: 72 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
37 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
39 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	128 mg/m² single, intravenous dose: 128 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
50 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	170 mg/m² single, intravenous dose: 170 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
60 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	226 mg/m² single, intravenous dose: 226 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
82 μM CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	300 mg/m² single, intravenous dose: 300 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
2000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	36 mg/m² single, intravenous dose: 36 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5800 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	72 mg/m² single, intravenous dose: 72 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5900 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	54 mg/m² single, intravenous dose: 54 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	72 mg/m² single, intravenous dose: 72 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	128 mg/m² single, intravenous dose: 128 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	170 mg/m² single, intravenous dose: 170 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	226 mg/m² single, intravenous dose: 226 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22000 μM × min CLINICAL TRIAL https://aacrjournals.org/clincancerres/article/13/7/2109/182362/A-Phase-I-Pharmacokinetic-and-Pharmacodynamic	300 mg/m² single, intravenous dose: 300 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PX-12 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP1B1 32

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006855	inconclusive [IC50 37.2212 uM]
CYP1B1 93	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12376470/	yes

PubMed

Title	Date	PubMed
Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner.	2008-05-21	18493321
2-[(1-methylpropyl)dithio]-1H-imidazole inhibits tubulin polymerization through cysteine oxidation.	2008-01	18202017
Gateways to clinical trials.	2007-06	17805439
A Phase I pharmacokinetic and pharmacodynamic study of PX-12, a novel inhibitor of thioredoxin-1, in patients with advanced solid tumors.	2007-04-01	17404093
A chemostat study of Streptomyces peucetius var. caesius N47.	2007-01	17115210
Drug evaluation: the thioredoxin inhibitor PX-12 in the treatment of cancer.	2006-12	17209529
The antitumor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl disulfide) decreases thioredoxin-1 and VEGF levels in cancer patient plasma.	2006-02	16459166
Cytotoxic and antiangiogenic activity of AW464 (NSC 706704), a novel thioredoxin inhibitor: an in vitro study.	2005-01-31	15655539
The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging.	2005-01-15	15701837
Gateways to clinical trials.	2004-04	15148527
Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women.	2003-07	12847685
The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation.	2003-03	12657718
Enhancement of metabolic oxidative stress-induced cytotoxicity by the thioredoxin inhibitor 1-methylpropyl 2-imidazolyl disulfide is mediated through the ASK1-SEK1-JNK1 pathway.	2002-12	12435809
The redox protein thioredoxin-1 regulates the constitutive and inducible expression of the estrogen metabolizing cytochromes P450 1B1 and 1A1 in MCF-7 human breast cancer cells.	2002-10	12376470
Normal-phase and stability-indicating reversed-phase high-performance liquid chromatographic methods for the determination of the novel antitumor agent: 1-methylpropyl-2-imidazolyldisulfide.	2002-03-05	11888051
Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication.	2001-10-01	11585774

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Mon Mar 31 18:09:20 GMT 2025` Edited by `admin` on `Mon Mar 31 18:09:20 GMT 2025`
Record UNII	8PQ9CZ8BTJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

1-METHYLPROPYL-2-IMIDAZOLYL DISULFIDE

Preferred Name

English

PX-12

Common Name

English

Code System Code Type Description

NCI_THESAURUS

C74082