Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors

被引：19

作者：

Huang, Shih-Chung ^{[1
]}

Adhikari, Sharmila ^{[1
]}

Brownell, James E. ^{[1
]}

Calderwood, Emily F. ^{[1
]}

Chouitar, Jouhara ^{[1
]}

D'Amore, Natalie Roy ^{[1
]}

England, Dylan B. ^{[1
]}

Foley, Klaudia ^{[1
]}

Harrison, Sean J. ^{[1
]}

LeRoy, Patrick J. ^{[1
]}

Lok, David ^{[1
]}

Lublinsky, Anna ^{[1
]}

Ma, Li-Ting ^{[1
]}

Menon, Saurabh ^{[1
]}

Yang, Yu ^{[1
]}

Zhang, Ji ^{[1
]}

Gould, Alexandra E. ^{[1
]}

机构：

[1] Takeda Pharmaceut Int Co, 40 Landsdowne St, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2020年 / 28卷 / 19期

关键词：

E1; enzyme; ATG7; inhibitor; Autophagy; AUTOPHAGY; UBIQUITIN;

D O I：

10.1016/j.bmc.2020.115681

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Autophagy is postulated to be required by cancer cells to survive periods of metabolic and/or hypoxic stress. ATG7 is the E1 enzyme that is required for activation of Ubl conjugation pathways involved in autophagosome formation. This article describes the design and optimization of pyrazolopyrimidine sulfamate compounds as potent and selective inhibitors of ATG7. Cellular levels of the autophagy markers, LC3B and NBR1, are regulated following treatment with these compounds.

引用

页数：21

共 50 条

[41] Nonredundant role of Atg7 in mitochondrial clearance during erythroid development
Mortensen, Monika
Simon, Anna Katharina
AUTOPHAGY, 2010, 6 (03) : 423 - 425
[42] ATG7 Gene Expression as a Novel Tissue Biomarker in Eosinophilic Esophagitis
Merves, Jamie F.
Whelan, Kelly A.
Benitez, Alain J.
Muir, Amanda B.
Furuta, Glenn T.
Wang, Mei-Lun
Falk, Gary W.
Spergel, Jonathan M.
Nakagawa, Hiroshi
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2016, 111 (01): : 151 - +
[43] Two different "tales" of ATG7: Clinical relevance to myelodysplastic syndromes
Ali, Abdullah M.
Raza, Azra
MOLECULAR & CELLULAR ONCOLOGY, 2016, 3 (05)
[44] ATG7 contributes to plant basal immunity towards fungal infection
Lenz, Heike D.
Vierstra, Richard D.
Nuernberger, Thorsten
Gust, Andrea A.
PLANT SIGNALING & BEHAVIOR, 2011, 6 (07) : 1040 - 1042
[45] Altered glycogen metabolism causes hepatomegaly following an Atg7 deletion
Kern, Lara
Spreckels, Johanne
Nist, Andrea
Stiewe, Thorsten
Skevaki, Chrysanthi
Greene, Brandon
Mernberger, Marco
Elsaesser, Hans-Peter
CELL AND TISSUE RESEARCH, 2016, 366 (03) : 651 - 665
[46] Biallelic ATG7 variants impair autophagy leading to neurological disease
Collier, Jack J.
Guissart, Claire
Olahova, Monika
Sasorith, Souphatta
Suomi, Fumi
Piron-Prunier, Florence
Zhang, David
Martinez-Lopez, Nuria
Leboucq, Nicolas
Bahr, Angela
Azzarello-Burri, Silvia
Reich, Selina
Schols, Ludger
Polvikoski, Tuomo
Rivier, Francois
Meyer, Pierre
Larrieu, Lise
Schaefer, Andrew
Alsaif, Hessa
Alyamani, Suad
Zuchner, Stephan
Barbosa, Ines
Deshpande, Charu
Pyle, Angela
Alkuraya, Fowzan
Ryten, Mina
Delahodde, Agnes
Rauch, Anita
Synofzik, Matthis
McFarland, Robert
McWilliams, Thomas G.
Koenig, Michel
Taylor, Robert W.
EUROPEAN JOURNAL OF HUMAN GENETICS, 2022, 30 (SUPPL 1) : 4 - 5
[47] ATG7 genetic variants predispose to severe fatty liver disease
Baselli, Guido
Pelusi, Serena
Ciociola, Ester
Dongiovanni, Paola
Maggioni, Marco
Bianco, Cristiana
Tavaglione, Federica
Cespiati, Annalisa
Mancina, Rosellina Margherita
Ostadreza, Mahnoosh
Miozzo, Monica
D'Ambrosio, Roberta
Petta, Salvatore
Miele, Luca
Gentilucci, Umberto Vespasiani
Federico, Alessandro
Pihlajamaki, Jussi
Bugianesi, Elisabetta
Fracanzani, Anna Ludovica
Reeves, Helen
Soardo, Giorgio
Prati, Daniele
Romeo, Stefano
Valenti, Luca
JOURNAL OF HEPATOLOGY, 2021, 75 : S261 - S262
[48] ATG7 and ATG14 restrict cytosolic and phagosomal Mycobacterium tuberculosis replication in human macrophages
Aylan, Beren
Bernard, Elliott M. M.
Pellegrino, Enrica
Botella, Laure
Fearns, Antony
Athanasiadi, Natalia
Bussi, Claudio
Santucci, Pierre
Gutierrez, Maximiliano G. G.
NATURE MICROBIOLOGY, 2023, 8 (05) : 803 - +
[49] m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7
Wang, Xinxia
Wu, Ruifan
Liu, Youhua
Zhao, Yuanling
Bi, Zhen
Yao, Yongxi
Liu, Qing
Shi, Hailing
Wang, Fengqin
Wang, Yizhen
AUTOPHAGY, 2020, 16 (07) : 1221 - 1235
[50] Defining the Sufficiency of Atg7 to Suppress Phenylephrine-induced Cardiac Hypertrophy
Tjeerdsma, Marcus
Froke, Levi
Freeling, Jessica
Pattison, Scott
CIRCULATION, 2014, 130

← 1 2 3 4 5 →