Synthesis of novel, thioredoxin - thioredoxin reductase inhibitors
|Adam Redzej 1, Ryszard Ostaszewski 1, Andżelika Szokalska 2, Jakub Gołąb 2|
1. Polish Academy of Science, Institute of Organic Chemistry, Kasprzaka 44/52, Warszawa 01-224, Poland
Thioredoxin-1 (Trx-1) is a protein which is over-expressed in many human tumors. The increased level of this protein in cells results in aggressive tumor growth and decreased patient survival.
Because of its role in promoting cell survival, proliferation and tumor angiogenesis, Trx-1 is an attractive molecular target. Therefore many studies have been done in order to obtain a selective inhibitor of Trx-1. One of such compounds is 2-[(1-Methylpropyl)dithio]-1H-imidazole (PX-12) (1). It is a small molecule which causes the oxidation of cysteine residues both in thioredoxin reductase (TR) and thioredoxin. But it irreversibly inhibits only Trx-1.  The second inhibitor of TR-Trx system is b,b-dibromoisobutyric acid methyl ester(2). 
Although biological activity of these two compounds is well described in literature, still not much is known about the mechanism of inhibition.
We will present the results of our studies on the synthesis of peptidomimetics possessing
 US Patent 5712417
Presentation: Poster at VI Multidyscyplinarna Konferencja Nauki o Leku, by Adam Redzej
See On-line Journal of VI Multidyscyplinarna Konferencja Nauki o Leku
Submitted: 2008-03-14 10:16 Revised: 2009-06-07 00:48