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Purity: ≥98%
PX-12 is an investigational antitumor agent acting as a potent thioredoxin-1 (Trx-1) inhibitor by irreversibly thioalkylating Cys73 of Trx-1. In HT-29 human colon carcinoma cells and MCF-7 human breast cancer, PX 12 prevented the hypoxia-induced increase in HIF-1 protein. Also, PX 12 decreased inducible nitric oxide synthase, HIF-1-trans-activating activity and VEGF formation. In immunodeficient mice bearing HT-29 human colon xenografts, PX 12 decreased the average tumor blood vessel permeability by 63% within 2 hours and returned to pretreatment values after 48 hours. PX 12 reduced tumor-derived VEGF and tumor after 24 hours.
| ln Vitro |
PX-12 has an IC50 of 1.9 μM for MCF-7 cells and 2.9 μM for HT-29 cells, respectively, which inhibits their growth[1]. By thio-alkylating the key cysteine residue (Cys73), which is situated outside of Trx-1's conserved redox catalytic region, PX-12 specifically lowers the activity of Trx-1. PX-12 influences several cell surface proteins' thiol oxidation status. Important surface receptors involved in platelet adhesion and activation are impacted, such as the von Willebrand factor receptor (GPIb) and the collagen receptor (GPVI). In whole blood, PX-12 prevents thrombus formation over Type I collagen when flow conditions are met[2]. Cellular redox protein thioredoxin-1 (Trx-1) up-regulates vascular endothelial growth factor and hypoxia-inducible factor-1α, suppresses apoptosis, and encourages the growth of tumors[3]. PX-12 has a dose- and time-dependent effect on the proliferation of colorectal cancer DLD-1 and SW620 cells. PX-12 inhibits the growth of new cell colonies and causes a G2/M phase arrest in the cell cycle. Treatment with PX-12 causes apoptosis. PX-12 prevents colon cancer cells from migrating and invading. PX-12 treatment enhances KLF17 mRNA expression while decreasing NOX1, CDH17, and S100A4 mRNA expression in cancer cells. In colorectal cancer cells, PX-12 reduces the expression of the S100A4 protein[4].
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| ln Vivo |
PX-12 has been evaluated in a phase I clinical trial including patients and has demonstrated in vivo anticancer efficacy against human tumor xenografts, including HT-29 colon cancer in SCID mice[3].
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| 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]. 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. |
| Molecular Formula |
C7H12N2S2
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| Molecular Weight |
188.31
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| CAS # |
141400-58-0
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| Related CAS # |
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| SMILES |
S(C([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])SC1=NC([H])=C([H])N1[H]
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| InChi Key |
BPBPYQWMFCTCNG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C7H12N2S2/c1-3-6(2)10-11-7-8-4-5-9-7/h4-6H,3H2,1-2H3,(H,8,9)
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| Chemical Name |
2-(sec-butyldisulfanyl)-1H-imidazole.
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (13.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (13.28 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (13.28 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: (saturation unknown) in (add these co-solvents sequentially from left to right, and one by one), |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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