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, Joao V.; Stewart, Hannah L.; Temple, Max; Thomas, Huw D.; Totobenazara, Jane; Tucker, Julie A.; Tudhope, Susan J.; Wang, Lan Z.; Bronowska, Agnieszka K.; Cano, Celine; Endicott, Jane A.; Golding, Bernard T.; Hardcastle, Ian R.; Hickson, Ian; Wedge, Stephen R.; Willmore, Elaine; Noble, Martin E. M.; Waring, Michael J. published the article 《An Alkynylpyrimidine-Based Covalent Inhibitor That Targets a Unique Cysteine in NF-κB-Inducing Kinase》. Keywords: cancer NIK covalent inhibitor SAR cysteine traps alkynyl heterocycles.They researched the compound: 5-Chloropicolinaldehyde( cas:31181-89-2 ).Product Details of 31181-89-2. Aromatic heterocyclic compounds can be divided into two categories: single heterocyclic and fused heterocyclic. In addition, there is a lot of other information about this compound (cas:31181-89-2) here.
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. Anal. 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 analogs 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.
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Phosphine ligand,
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate