896459-91-9Relevant academic research and scientific papers
Synthesis of isosteric selenium analog of the PPARβ/δ agonist GW501516 and comparison of biological activity
Sharma, Arun K.,Sk, Ugir Hossain,He, Pengfei,Peters, Jeffrey M.,Amin, Shantu
experimental part, p. 4050 - 4052 (2010/09/04)
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and members of the nuclear hormone receptor superfamily. Herein, we describe an efficient synthesis of a novel isosteric selenium analog of the highly specific PPARβ/δ ligand 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5-yl)-meth ylsulfanyl)phenoxy-acetic acid (GW501516; 1). The study examined the efficiency of the novel selenium analog 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-selenazol-5-yl)-me thylsulfanyl)phenoxy-acetic acid (2) to activate PPARβ/δ and the effect of ligand activation of PPARβ/δ on cell proliferation and target gene expression in human HaCaT keratinocytes. The results showed that similar to GW501516, the Se-analog 2 increased expression of the known PPARβ/δ target gene angiopoietin-like protein 4 (ANGPTL4); the compound 2 was comparable in efficacy as compared to GW501516. Consistent with a large body of evidence, the Se-analog inhibited cell proliferation in HaCaT keratinocytes similar to that observed with GW501516. In summary, the novel Se-analog 2 has been developed as a potent PPARβ/δ ligand that may possess additional anti-cancer properties of selenium.
Selective peroxisome proliferator-activated receptor δ isosteric selenium agonists as potent anti-atherogenic agents in vivo
Chin, Jungwook,Hong, Jun Young,Lee, Jaehwan,Hwang, Hoosang,Ko, Hyunsil,Choi, Hyukjae,Hahn, Dongyup,Ko, Jaeyoung,Nam, Sang-Jip,Tak, Jungae,Ham, Jungyeob,Kang, Heonjoong
supporting information; experimental part, p. 7239 - 7242 (2011/01/03)
We report the synthesis and in vivo activity of a novel anti-atherogenic agent, isosteric selenium PPARδ-selective ligand. This ligand did not cause significant body or liver weight changes and did not have obvious adverse effects on intestinal polyp formation. Our overall results clearly demonstrate that PPARδ is a viable drug candidate for targeting and treating atherosclerosis.
