Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer was written by Langston, Steven P.;Grossman, Stephen;England, Dylan;Afroze, Roushan;Bence, Neil;Bowman, Douglas;Bump, Nancy;Chau, Ryan;Chuang, Bei-Ching;Claiborne, Christopher;Cohen, Larry;Connolly, Kelly;Duffey, Matthew;Durvasula, Nitya;Freeze, Scott;Gallery, Melissa;Galvin, Katherine;Gaulin, Jeffrey;Gershman, Rachel;Greenspan, Paul;Grieves, Jessica;Guo, Jianping;Gulavita, Nanda;Hailu, Shumet;He, Xingyue;Hoar, Kara;Hu, Yongbo;Hu, Zhigen;Ito, Mitsuhiro;Kim, Mi-Sook;Lane, Scott Weston;Lok, David;Lublinsky, Anya;Mallender, William;McIntyre, Charles;Minissale, James;Mizutani, Hirotake;Mizutani, Miho;Molchinova, Nina;Ono, Koji;Patil, Ashok;Qian, Mark;Riceberg, Jessica;Shindi, Vaishali;Sintchak, Michael D.;Song, Keli;Soucy, Teresa;Wang, Yana;Xu, He;Yang, Xiaofeng;Zawadzka, Agatha;Zhang, Ji;Pulukuri, Sai M.. And the article was included in Journal of Medicinal Chemistry in 2021.Computed Properties of C8H9Cl This article mentions the following:
SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclin. tumor models, culminating in the identification of the clin. mol. TAK-981. In the experiment, the researchers used many compounds, for example, 1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9Computed Properties of C8H9Cl).
1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Computed Properties of C8H9Cl
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics