75315-97-8Relevant articles and documents
Antibody-mediated delivery of chimeric protein degraders which target estrogen receptor alpha (ERα)
Dragovich, Peter S.,Adhikari, Pragya,Blake, Robert A.,Blaquiere, Nicole,Chen, Jinhua,Cheng, Yun-Xing,den Besten, Willem,Han, Jinping,Hartman, Steven J.,He, Jintang,He, Mingtao,Rei Ingalla, Ellen,Kamath, Amrita V.,Kleinheinz, Tracy,Lai, Tommy,Leipold, Douglas D.,Li, Chun Sing,Liu, Qi,Lu, Jiawei,Lu, Ying,Meng, Fanwei,Meng, Lingyao,Ng, Carl,Peng, Kaishan,Lewis Phillips, Gail,Pillow, Thomas H.,Rowntree, Rebecca K.,Sadowsky, Jack D.,Sampath, Deepak,Staben, Leanna,Staben, Steven T.,Wai, John,Wan, Kunpeng,Wang, Xinxin,Wei, BinQing,Wertz, Ingrid E.,Xin, Jianfeng,Xu, Keyang,Yao, Hui,Zang, Richard,Zhang, Donglu,Zhou, Hao,Zhao, Yongxin
supporting information, (2020/01/08)
Chimeric molecules which effect intracellular degradation of target proteins via E3 ligase-mediated ubiquitination (e.g., PROTACs) are currently of high interest in medicinal chemistry. However, these entities are relatively large compounds that often possess molecular characteristics which may compromise oral bioavailability, solubility, and/or in vivo pharmacokinetic properties. Accordingly, we explored whether conjugation of chimeric degraders to monoclonal antibodies using technologies originally developed for cytotoxic payloads might provide alternate delivery options for these novel agents. In this report we describe the construction of several degrader-antibody conjugates comprised of two distinct ERα-targeting degrader entities and three independent ADC linker modalities. We subsequently demonstrate the antigen-dependent delivery to MCF7-neo/HER2 cells of the degrader payloads that are incorporated into these conjugates. We also provide evidence for efficient intracellular degrader release from one of the employed linkers. In addition, preliminary data are described which suggest that reasonably favorable in vivo stability properties are associated with the linkers utilized to construct the degrader conjugates.
Synthesis and intrinsic blue fluorescence study of hyperbranched poly(ester-amide-ether)
Zhang, Yong,Fu, Qi,Shi, Wenfang
experimental part, p. 2452 - 2460 (2011/10/02)
A series of hyperbranched poly(ester-amide-ether)s (H-PEAEs) were synthesized via the A2+CB3 approach by the self-transesterification of ethyl ester-amide-ethers end-capped with three hydroxyl groups and ethyl ester group at two terminals. The molecular structures were characterized with 1H NMR and FT-IR spectroscopy. The number average molecular weights were estimated by GPC analysis to possess bimodal wide distribution from 1.57 to 2.09. The strong inherent blue fluorescence was observed at 330 nm for excitation and 390 nm for emission. Moreover, the emission intensity and fluorescence quantum yield increased along with the incorporated ether chain length, as well as almost linearly with the H-PEAE concentration in an aqueous solution. For comparing the fluorescence performance, the linear poly(ester-amide-ether) (L-PEAE) and hyperbranched poly(ester-amide) (H-PEA) were synthesized. The results showed that the coexistence of ether bond and carboxyl group in the molecular chain was essential for generating the strong fluorescence. However, the compact backbone of H-PEAE would be propitious to the enhancement of fluorescence properties.
