81168-10-7Relevant academic research and scientific papers
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.
, 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.
HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF SUMO ACTIVATING ENZYME
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Paragraph 00321; 00323, (2016/01/25)
Disclosed are chemical entities which are compounds of formula (I); or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra', Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.
Safety-catch linkers
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, (2008/06/13)
Safety-catch linkers and methods for use of safety-catch linkers in solid phase and combinatorial solid phase synthesis are provided. Safety-catch linkers covalently bonded to solid supports are also provided. The safety-catch linkers are stable to a wide variety of synthetic protocols so that substrates, such as amines, thiols and alcohols, are cleaved from the linkers under mild conditions. The safety-catch linkers are useful in solid phase synthesis and modification of natural products and other complex organic substrates.
Synthesis of 3,9b-Dihydro-5H-pyrroloisoindoles and 3,5,6,10b-Tetrahydropyrroloisoquinolines with 1,3-Dipolar Cycloaddition Reactions.
Anderson, Wayne K.,Kinder, Frederick R.
, p. 975 - 979 (2007/10/02)
The title classes of compounds have been prepared using a sequence of two ring-forming reactions.Initial 1,3-dipolar cycloaddition with an azomethine ylide gave N-acylated 3-pyrrolines which were further elaborated to the target compounds by a tandem deprotection/cyclization reaction.
