PX 12

Cas No.:	141400-58-0
Chemical Name:	2-[(1-Methylpropyl)dithio]-1H-imidazole; IV-2
Synonyms:	PX-12,PX12
SMILES:	CCC(SSC1=NC=CN1)C
Formula:	C7H12N2S2
M.Wt:	188.31
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

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.
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].
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].