PX-12

Names

[ Name ]:
PX-12

[Synonym ]:
2-(butan-2-yldisulfanyl)-1H-imidazole
IV-2 compound
UNII:8PQ9CZ8BTJ
1-methylpropyl 2-imidazolyl disulfide
PX 12
1-methyl-1-propyl 2-imidazolyl disulfide
2-(sec-Butyldisulfanyl)-1H-imidazole
1-methylpropyl 2-mercaptoimidazolyl disulfide
2-[(1-Methylpropyl)dithio]-1H-imidazole
1H-Imidazole, 2-[(1-methylpropyl)dithio]-
PX-12

Biological Activity

[Description]:

PX-12(IV-2) is an irreversible inhibitor of Thioredoxin-1 (Trx-1); inhibits the growth of MCF-7 and HT-29 cells with IC50 values of 1.9 and 2.9 μM, respectively.

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Cancer

[Target]

IC50: 1.9 (MCF-7), 2.9 μM (HT-29 cells)[1]

[In Vitro]

PX-12 inhibits the growth of MCF-7 and HT-29 cells with IC50 values of 1.9 and 2.9 μM, respectively[1]. PX-12 particularly reduces the activity of Trx-1 by means of thio-alkylating critical cysteine residue (Cys73) which is located in the outside the conserved redox catalytic site of Trx-1. PX-12 affects the oxidation state of thiols in a number of cell surface proteins. Key surface receptors for platelet adhesion and activation are affected, including the collagen receptor GPVI and the von Willebrand factor receptor, GPIb. PX-12 inhibits thrombus formation over Type I collagen in whole blood under flow conditions[2]. Thioredoxin-1 (Trx-1) is a cellular redox protein that promotes tumor growth, inhibits apoptosis, and up-regulates hypoxia-inducible factor-1α and vascular endothelial growth factor[3]. PX-12 inhibits the growth of colorectal cancer DLD-1 and SW620 cells in a dose- and time-dependent manner. PX-12 reduces cell colony formation and induced a G2/M phase arrest of the cell cycle. PX-12 treatment induces apoptosis. PX-12 inhibits colorectal cancer cell migration and invasion. Treatment of cancer cells with PX-12 reduces NOX1, CDH17 and S100A4 mRNA expression, and increases KLF17 mRNA expression. PX-12 decreases S100A4 protein expression in the colorectal cancer cells[4].

[In Vivo]

PX-12 has been shown to have in vivo antitumor activity against human tumor xenografts including HT-29 colon cancer in SCID mice and has been tested in a phase I clinical trial in patients[3].

[References]

[1]. Welsh SJ, et al. The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation. Mol Cancer Ther. 2003 Mar;2(3):235-43.

[2]. Metcalfe C, et al. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation.PLoS One. 2016 Oct 7;11(10):e0163006

[3]. Ramanathan RK, et al. A Phase I pharmacokinetic and pharmacodynamic study of PX-12, a novel inhibitor of thioredoxin-1, in patients with advanced solid tumors. Clin Cancer Res. 2007 Apr 1;13(7):2109-14.

[4]. Wang F, et al. Thioredoxin-1 inhibitor, 1-methylpropyl 2-imidazolyl disulfide, inhibits the growth, migration and invasion of colorectal cancer cell lines. Oncol Rep. 2015 Feb;33(2):967-73.

[5]. Lou M, et al. Physical interaction between human ribonucleotide reductase large subunit and thioredoxin increases colorectal cancer malignancy. J Biol Chem. 2017 Jun 2;292(22):9136-9149.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
330.0±25.0 °C at 760 mmHg

[ Molecular Formula ]:
C₇H₁₂N₂S₂

[ Molecular Weight ]:
188.314

[ Flash Point ]:
153.4±23.2 °C

[ Exact Mass ]:
188.044189

[ PSA ]:
79.28000

[ LogP ]:
3.40

[ Vapour Pressure ]:
0.0±0.7 mmHg at 25°C

[ Index of Refraction ]:
1.590

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2933290090

Customs

[ HS Code ]: 2933290090

[ Summary ]:
2933290090. other compounds containing an unfused imidazole ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

The overexpression and nuclear translocation of Trx-1 during hypoxia confers on HepG2 cells resistance to DDP, and GL-V9 reverses the resistance by suppressing the Trx-1/Ref-1 axis.

Free Radic. Biol. Med. 82 , 29-41, (2015)

Microenvironmental hypoxia gives many tumor cells the capacity for drug resistance. Thioredoxin family members play critical roles in the regulation of cellular redox homeostasis in a stressed environ...

Inhibition of thioredoxin 1 leads to apoptosis in drug-resistant multiple myeloma.

Oncotarget 6 , 15410-24, (2015)

Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant accumulation of clonal plasma cells in the bone marrow. Despite recent advancement in anti-myeloma treatment, MM remai...

Thioredoxin is involved in endothelial cell extracellular transglutaminase 2 activation mediated by celiac disease patient IgA.

PLoS ONE 8 , e77277, (2013)

To investigate the role of thioredoxin (TRX), a novel regulator of extracellular transglutaminase 2 (TG2), in celiac patients IgA (CD IgA) mediated TG2 enzymatic activation.TG2 enzymatic activity was ...