Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation was written by Ohoka, Nobumichi;Morita, Yoko;Nagai, Katsunori;Shimokawa, Kenichiro;Ujikawa, Osamu;Fujimori, Ikuo;Ito, Masahiro;Hayase, Youji;Okuhira, Keiichiro;Shibata, Norihito;Hattori, Takayuki;Sameshima, Tomoya;Sano, Osamu;Koyama, Ryokichi;Imaeda, Yasuhiro;Nara, Hiroshi;Cho, Nobuo;Naito, Mikihiko. And the article was included in Journal of Biological Chemistry in 2018.Formula: C13H12O2 The following contents are mentioned in the article:
Aberrant expression of proteins often underlies many diseases, including cancer. A recently developed approach in drug development is small mol.-mediated, selective degradation of dysregulated proteins. The authors have devised a protein-knockdown system that utilizes chimeric mols. termed specific and nongenetic IAP-dependent protein erasers (SNIPERs) to induce ubiquitylation and proteasomal degradation of various target proteins. SNIPER(ER)-87 consists of an inhibitor of apoptosis protein (IAP) ligand LCL161 derivative that is conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen by a PEG linker, and the authors have previously reported that this SNIPER efficiently degrades the ERα protein. Here, the authors report that derivatization of the IAP ligand module yields SNIPER(ER)s with superior protein-knockdown activity. These improved SNIPER(ER)s exhibited higher binding affinities to IAPs and induced more potent degradation of ERα than does SNIPER(ER)-87. Further, they induced simultaneous degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and delayed degradation of X-linked IAP (XIAP). Notably, these reengineered SNIPER(ER)s efficiently induced apoptosis in MCF-7 human breast cancer cells that require IAPs for continued cellular survival. The authors found that one of these mols., SNIPER(ER)-110, inhibits the growth of MCF-7 tumor xenografts in mice more potently than the previously characterized SNIPER(ER)-87. Mechanistic anal. revealed that the authors’ novel SNIPER(ER)s preferentially recruit XIAP, rather than cIAP1, to degrade ERα. The authors’ results suggest that derivatized IAP ligands could facilitate further development of SNIPERs with potent protein-knockdown and cytocidal activities against cancer cells requiring IAPs for survival. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2Formula: C13H12O2).
4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Esters contain a carbonyl center, which gives rise to 120° C–C–O and O–C–O angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Formula: C13H12O2
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem