120539-91-5Relevant articles and documents
A strategic approach to [6,6]-bicyclic lactones: Application towards the CD fragment of DHβE
Jepsen, Tue Heesgaard,Glibstrup, Emil,Crestey, Fran?ois,Jensen, Anders A.,Kristensen, Jesper Langgaard
, p. 988 - 994 (2017)
We report an effective synthetic protocol to access [6,6]-bicyclic lactone moieties through a regio- and stereoselective intramolecular Mizoroki–Heck cross-coupling reaction followed by a 6π-electrocyclization. This method enabled the first synthesis of t
An Alkynylpyrimidine-Based Covalent Inhibitor That Targets a Unique Cysteine in NF-κB-Inducing Kinase
Al-Khawaldeh, Islam,Al Yasiri, Mohammed J.,Aldred, Gregory G.,Basmadjian, Christine,Bordoni, Cinzia,Harnor, Suzannah J.,Heptinstall, Amy B.,Hobson, Stephen J.,Jennings, Claire E.,Khalifa, Shaimaa,Lebraud, Honorine,Martin, Mathew P.,Miller, Duncan C.,Shrives, Harry J.,de Souza, Jo?o V.,Stewart, Hannah L.,Temple, Max,Thomas, Huw D.,Totobenazara, Jane,Tucker, Julie A.,Tudhope, Susan J.,Wang, Lan Z.,Bronowska, Agnieszka K.,Cano, Céline,Endicott, Jane A.,Golding, Bernard T.,Hardcastle, Ian R.,Hickson, Ian,Wedge, Stephen R.,Willmore, Elaine,Noble, Martin E. M.,Waring, Michael J.
, p. 10001 - 10018 (2021)
NF-κB-inducing kinase (NIK) is a key enzyme in the noncanonical NF-κB pathway, of interest in the treatment of a variety of diseases including cancer. Validation of NIK as a drug target requires potent and selective inhibitors. The protein contains a cysteine residue at position 444 in the back pocket of the active site, unique within the kinome. Analysis of existing inhibitor scaffolds and early structure-activity relationships (SARs) led to the design of C444-targeting covalent inhibitors based on alkynyl heterocycle warheads. Mass spectrometry provided proof of the covalent mechanism, and the SAR was rationalized by computational modeling. Profiling of more potent analogues in tumor cell lines with constitutively activated NIK signaling induced a weak antiproliferative effect, suggesting that kinase inhibition may have limited impact on cancer cell growth. This study shows that alkynyl heterocycles are potential cysteine traps, which may be employed where common Michael acceptors, such as acrylamides, are not tolerated.
Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and beyond
Wu, Chien-Huang,Song, Jen-Shin,Kuan, Hsuan-Hao,Wu, Szu-Huei,Chou, Ming-Chen,Jan, Jiing-Jyh,Tsou, Lun K.,Ke, Yi-Yu,Chen, Chiung-Tong,Yeh, Kai-Chia,Wang, Sing-Yi,Yeh, Teng-Kuang,Tseng, Chen-Tso,Huang, Chen-Lung,Wu, Mine-Hsine,Kuo, Po-Chu,Lee, Chia-Jui,Shia, Kak-Shan
supporting information, p. 818 - 833 (2018/02/17)
The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from b
