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.
For research use only. We do not sell to patients.
PX-12 Chemical Structure
CAS No. : 141400-58-0
This product is a controlled substance and not for sale in your territory.
Based on 7 publication(s) in Google Scholar
PX-12 purchased from MedChemExpress. Usage Cited in:
J Biol Chem. 2017 Jun 2;292(22):9136-9149.
[Abstract]
The plate clone formation of SW480 and SW620 cells with Gemcitabine (8 nM in SW480 and 16 nM in SW620) and/or PX-12 (4 μM in SW480 and 8 μM in SW620).
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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.
IC50 & 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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PX-12 Related Antibodies
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight
188.31
Formula
C7H12N2S2
CAS No.
141400-58-0
Appearance
Solid
Color
White to light yellow
SMILES
CC(CC)SSC1=NC=CN1
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvent & Solubility
In Vitro:
Ethanol : 50 mg/mL (265.52 mM; Need ultrasonic)
DMSO : ≥ 44.7 mg/mL (237.37 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
5.3104 mL
26.5520 mL
53.1039 mL
5 mM
1.0621 mL
5.3104 mL
10.6208 mL
10 mM
0.5310 mL
2.6552 mL
5.3104 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
Protocol 3
Add each solvent one by one: 10% EtOH 40% PEG300 5% Tween-80 45% Saline
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 4
Add each solvent one by one: 10% EtOH 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[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.
[Content Brief]
[2]. 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.
[Content Brief]
[3]. Metcalfe C, et al. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation.
PLoS One. 2016 Oct 7;11(10):e0163006
[Content Brief]
[4]. 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.
[Content Brief]
[5]. 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.
[Content Brief]
[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]. 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.
[3]. Metcalfe C, et al. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation.
PLoS One. 2016 Oct 7;11(10):e0163006
[4]. 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.
[5]. 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.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO / Ethanol
1 mM
5.3104 mL
26.5520 mL
53.1039 mL
132.7598 mL
5 mM
1.0621 mL
5.3104 mL
10.6208 mL
26.5520 mL
10 mM
0.5310 mL
2.6552 mL
5.3104 mL
13.2760 mL
15 mM
0.3540 mL
1.7701 mL
3.5403 mL
8.8507 mL
20 mM
0.2655 mL
1.3276 mL
2.6552 mL
6.6380 mL
25 mM
0.2124 mL
1.0621 mL
2.1242 mL
5.3104 mL
30 mM
0.1770 mL
0.8851 mL
1.7701 mL
4.4253 mL
40 mM
0.1328 mL
0.6638 mL
1.3276 mL
3.3190 mL
50 mM
0.1062 mL
0.5310 mL
1.0621 mL
2.6552 mL
60 mM
0.0885 mL
0.4425 mL
0.8851 mL
2.2127 mL
80 mM
0.0664 mL
0.3319 mL
0.6638 mL
1.6595 mL
100 mM
0.0531 mL
0.2655 mL
0.5310 mL
1.3276 mL
PX-12 Related Classifications
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.