Exploitation of the Ability of γ-Tocopherol to Facilitate Membrane Co-localization of Akt and PHLPP1 to Develop PHLPP1-Targeted Akt Inhibitors was written by Yan, Ribai;Chuang, Hsiao-Ching;Kapuriya, Naval;Chou, Chih-Chien;Lai, Po-Ting;Chang, Hsin-Wen;Yang, Chia-Ning;Kulp, Samuel K.;Chen, Ching-Shih. And the article was included in Journal of Medicinal Chemistry in 2015.Product Details of 28322-40-9 This article mentions the following:
Previously, the authors reported that Akt inactivation by γ-tocopherol in PTEN-neg. prostate cancer cells resulted from its unique ability to facilitate membrane colocalization of Akt and PHLPP1 (PH domain leucine-rich repeat protein phosphatase isoform 1), a Ser473-specific Akt phosphatase, through pleckstrin homol. (PH) domain binding. This finding provided a basis for exploiting γ-tocopherol to develop a novel class of PHLPP1-targeted Akt inhibitors. Here, the authors used I (γ-VE5), a side chain-truncated γ-tocopherol derivative, as a scaffold for lead optimization. The proof-of-concept of this structural optimization was obtained by II, which exhibited higher antitumor efficacy than I in PTEN-neg. cancer cells through PHLPP1-facilitated Akt inactivation. Like I, II preferentially recognized the PH domains of Akt and PHLPP1, as its binding affinities for other PH domains, including those of ILK and PDK1, were an order-of-magnitude lower. Moreover, II was orally active in suppressing xenograft tumor growth in nude mice, which underlines the translational potential of this new class of Akt inhibitor in PTEN-deficient cancers. In the experiment, the researchers used many compounds, for example, Isopentyltriphenylphosphonium bromide (cas: 28322-40-9Product Details of 28322-40-9).
Isopentyltriphenylphosphonium bromide (cas: 28322-40-9) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Product Details of 28322-40-9
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary