CAS 141400-58-0|PX-12
| Common Name | PX-12 | ||
|---|---|---|---|
| CAS Number | 141400-58-0 | Molecular Weight | 188.314 |
| Density | 1.2±0.1 g/cm3 | Boiling Point | 330.0±25.0 °C at 760 mmHg |
| Molecular Formula | C7H12N2S2 | Melting Point | / |
| MSDS | ChineseUSA | Flash Point | 153.4±23.2 °C |
| Symbol | GHS07 | Signal Word | Warning |
Names
| Name | 2-(butan-2-yldisulfanyl)-1H-imidazole |
|---|---|
| Synonym | More Synonyms |
PX-12 BiologicalActivity
| 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 >>OthersResearch 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. |
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 |
| InChIKey | BPBPYQWMFCTCNG-UHFFFAOYSA-N |
| SMILES | CCC(C)SSc1ncc[nH]1 |
| Storage condition | -20℃ |
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% |
Articles4
More 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 ... |
Synonyms
| 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 |
