product name PX-12
Description: PX-12 is a potent thioredoxin-1 (Trx-1) inhibitor by irreversibly thioalkylation of 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.
References: Mol Cancer Ther. 2003 Mar;2(3):235-43; Cancer Chemother Pharmacol. 2011 Aug;68(2):405-13.
188.31
Formula
C7H12N2S2
CAS No.
141400-58-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 38 mg/mL (201.8 mM)
Water: <1 mg/mL
Ethanol: 38 mg/mL (201.8 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In MCF-7 and HT-29 cells, PX-12 prevents the hypoxia (1% oxygen)-induced increase in HIF-1alpha protein, and decreases HIF-1-trans-activating activity, VEGF formation, and inducible nitric oxide synthase. PX-12 also inhibits the growth of MCF-7 and HT-29 cells with IC50s of 1.9 μM and 2.9μM, respectively. PX-12 also inhibits HIF-1α protein levels through an Nrf2/PMF-1-mediated increase. In A549 cells, PX-12 inhibits cell growth via G2/M phase arrest, and Bax-mediated and ROS-dependent apoptosis. In hepatocelluar carcinoma cells, PX-12 exerts a synergistic effect with 5-FU to significantly suppress tumorigenicity. Kinase Assay: Cell Assay: Cell growth is measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cells are exposed to a range of concentrations of PX-12 or pleurotin for 16 h in air or hypoxia (1% oxygen). The cells are then washed with warm drug-free medium and grown in air for the remainder of the 72-h incubation. |
|---|---|
| In Vivo | In mice bearing MCF-7 tumor xenografts, PX-12 (12 mg/kg, i.p.) decreases HIF-1α and VEGF protein levels and microvessel density. |
| Animal model | Mice bearing MCF-7 tumor xenografts |
| Formulation & Dosage | Dissolved in 0.01 N HCl, polyethylene glycol-400 (2.0 mg/ml); 12 mg/kg; i.p. |
| References | Mol Cancer Ther. 2003 Mar;2(3):235-43; Cancer Chemother Pharmacol. 2011 Aug;68(2):405-13. |
