117954-70-8Relevant articles and documents
Discovery of TAK-981, a First-in-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer
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.
supporting information, p. 2501 - 2520 (2021/04/02)
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 enzymatic 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 preclinical tumor models, culminating in the identification of the clinical molecule TAK-981.
Proton-exchanged montmorillonite-mediated reactions of hetero-benzyl acetates: Application to the synthesis of Zafirlukast
Yang, Lei,Chen, Xuan,Ni, Kaidong,Li, Yuansheng,Wu, Jianhong,Chen, Weilin,Ji, Yin,Feng, Lili,Li, Fei,Chen, Dongyin
supporting information, (2020/06/28)
Proton-exchanged montmorillonite (H-mont) with outstanding surface characteristics can provide abundant acidic sites in the mesopores, and serve as an efficient heterogeneous catalyst for the synthesis of heterocycle-containing diarylmethanes via Friedel-Crafts-like alkylation of (hetero)arenes by heterobenzyl acetates under mild reaction conditions without requiring any additives or an inert atmosphere. Using this strategy, the gram-scale synthesis of indole-containing diarylmethane 13 has been accomplished in good yield for the preparation of Zafirlukast. In addition, H-mont can be applied to the nucleophilic substitution reactions of heterobenzyl acetate 5p with a variety of alcohols and 1,3-dicarbonyl compounds.
Gold(I)-catalyzed dearomative rautenstrauch rearrangement: Enantioselective access to cyclopenta[ b ]indoles
Zi, Weiwei,Wu, Hongmiao,Toste, F. Dean
supporting information, p. 3225 - 3228 (2015/03/30)
A highly enantioselective dearomative Rautenstrauch rearrangement catalyzed by cationic (S)-DTBM-Segphosgold(I) is reported. This reaction provides a straightforward method to prepare enantioenriched cyclopenta[b]indoles. These studies show vast differenc
