143571-14-6Relevant articles and documents
Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: Effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of Src homology 2 domain-containing protein tyrosine phosphatase-2 activity
Dawson, Marcia I.,Xia, Zebin,Jiang, Tao,Ye, Mao,Fontana, Joseph A.,Farhana, Lulu,Patel, Bhaumik,Li, Ping Xue,Bhuiyan, Mohammad,Pellicciari, Roberto,Macchiarulo, Antonio,Nuti, Roberto,Zhang, Xiao-Kun,Han, Young-Hoon,Tautz, Lutz,Hobbs, Peter D.,Jong, Ling,Waleh, Nahid,Chao, Wan-Ru,Feng, Gen-Sheng,Pang, Yuhong,Su, Ying
supporting information; experimental part, p. 5650 - 5662 (2009/08/09)
(E)-4-[3-(1-Adamantyl)-4′-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) induces the cell-cycle arrest and apoptosis of leukemia and cancer cells. Studies demonstrated that 3-Cl-AHPC bound to the atypical orphan nuclear receptor small heterodimer partner (SHP). Although missing a DNA-binding domain, SHP heterodimerizes with the ligand-binding domains of other nuclear receptors to repress their abilities to induce or inhibit gene expression. 3-Cl-AHPC analogues having the 1-adamantyl and phenolic hydroxyl pharmacophoric elements replaced with isosteric groups were designed, synthesized, and evaluated for their inhibition of proliferation and induction of human cancer cell apoptosis. Structure-anticancer activity relationship studies indicated the importance of both groups to apoptotic activity. Docking of 3-Cl-AHPC and its analogues to an SHP computational model that was based on the crystal structure of ultraspiracle complexed with 1-stearoyl-2-palmitoylglycero-3-phosphoethanolamine suggested why these 3-Cl-AHPC groups could influence SHP activity. Inhibitory activity against Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp-2) was also assessed. The most active Shp-2 inhibitor was found to be the 3′-(3,3-dimethylbutynyl) analogue of 3-Cl-AHPC.