42749-28-0Relevant articles and documents
Radioiodinated progesterone derivative for progesterone receptor targeting with enhanced nucleus uptake via phenylboronic acid conjugation
Gao, Fei,Peng, Chenyu,Li, Jindian,Zhuang, Rongqiang,Guo, Zhide,Xu, Duo,Su, Xinhui,Zhang, Xianzhong
, p. 301 - 309 (2019)
A novel 131I-radiolabeled probe with aromatic boronate motif (131I-EIPBA) was designed to target progesterone receptor (PR)–positive breast cancer with enhanced nucleus uptake. Acetylene progesterone was conjugated with pegylated phe
Alternative reagents for methotrexate as immobilizing anchor moieties in the optimization of MASPIT: Synthesis and biological evaluation
De Clercq, Dries J.H.,Risseeuw, Martijn D.P.,Karalic, Izet,De Smet, Anne-Sophie,Defever, Dieter,Tavernier, Jan,Lievens, Sam,Van Calenbergh, Serge
, p. 834 - 843 (2015)
We report the evaluation of two alternative chemical dimerizer approaches aimed at increasing the sensitivity of MASPIT, a three-hybrid system that enables small-molecule target protein profiling in intact human cells. To circumvent the potential limitati
Discovery of novel potent covalent inhibitor-based EGFR degrader with excellent in vivo efficacy
Cui, Jiaqi,Du, Yu,Huang, Lei,Niu, Jing,Shi, Shi,Xu, Yungen,Zhu, Qihua
supporting information, (2022/01/26)
Although several Epidermal growth factor receptor (EGFR) inhibitors have been approved for the treatment of non-small-cell lung cancers (NSCLC), acquired drug resistance and side effects largely encumbered their application in clinic. The emerging technology Proteolysis targeting chimera (PROTAC) could be an alternative strategy to overcome these problems. Here, we reported the discovery of Dacomitinib-based EGFR degraders. Promising compound 13 can effectively induce degradation of EGFRdel19 with DC50 value of 3.57 nM in HCC-827 cells, but not to other EGFR mutant, wild-type EGFR protein and the same family receptors (HER2 and HER4). Of note, 13 is the first EGFR-PROTAC to evaluate antitumor effect in vivo, and exhibited excellent antitumor efficacy (TGI = 90%) at a dose of 30 mg/kg without causing observable toxic effects. The preliminary mechanism study demonstrated that 13 can efficiently induce EGFR protein degradation through ubiquitin proteasome pathway and inhibit phosphorylation of downstream pathways in vitro and in vivo, which indicated that 13 exerted antitumor effect by degradation of EGFR protein in tumor tissue. Overall, our study provided further evidence to validate EGFR-PROTACs as a promising strategy for lung cancer therapy.
COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION
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Page/Page column 49; 50, (2021/06/11)
The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.
PROTAC compound for targeted degradation of IDO1, and preparation method and application thereof
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Paragraph 0024-0026; 0038-0041, (2020/06/17)
The invention provides a PROTAC compound represented by formula I and used for targeted degradation of IDO1, and a pharmaceutically acceptable salt, a hydrate or a solvate thereof. In the formula I, Xrepresents -CH2 or -C = O, Y represents -CH2 or -C= O, and n is a natural number from 2 to 9. The PROTAC compound for targeted degradation of the IDO1 has efficient activity of targeted degradation of the IDO1 protein.
