Covalent PROTACs: the best of both worlds?

被引：31

作者：

Grimster, Neil P. ^{[1
]}

机构：

[1] AstraZeneca, Oncol R&D, Waltham, MA 02451 USA

来源：

RSC MEDICINAL CHEMISTRY | 2021年 / 12卷 / 09期

关键词：

PROTEIN-DEGRADATION; DISCOVERY; INHIBITOR;

D O I：

10.1039/d1md00191d

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：

Covalent PROTACs combine the cutting edge research areas of targeted covalent inhibitors (TCIs) and proteolysis targeting chimeras (PROTACs). This nascent field of research has already demonstrated several interesting findings, and holds an immense amount of potential to expand the druggable proteome. In this opinion, we present some of these intriguing early findings and discuss the potential advantages and disadvantages of this approach.

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页码：1452 / 1458

页数：7

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共 36 条

[1] Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs [J].

Alabi, Shanique B. ;

Crews, Craig M. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 296 (296)

[2] Proteome-wide covalent ligand discovery in native biological systems [J].

Backus, Keriann M. ;

Correia, Bruno E. ;

Lum, Kenneth M. ;

Forli, Stefano ;

Horning, Benjamin D. ;

Gonzalez-Paez, Gonzalo E. ;

Chatterjee, Sandip ;

Lanning, Bryan R. ;

Teijaro, John R. ;

Olson, Arthur J. ;

Wolan, Dennis W. ;

Cravatt, Benjamin F. .

NATURE, 2016, 534 (7608) :570-+

[3] Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile [J].

Barf, Tjeerd ;

Covey, Todd ;

Izumi, Raquel ;

van de Kar, Bas ;

Gulrajani, Michael ;

van Lith, Bart ;

van Hoek, Maaike ;

de Zwart, Edwin ;

Mittag, Diana ;

Demont, Dennis ;

Verkaik, Saskia ;

Krantz, Fanny ;

Pearson, Paul G. ;

Ulrich, Roger ;

Kaptein, Allard .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2017, 363 (02) :240-252

[4] Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs [J].

Bond, Michael J. ;

Chu, Ling ;

Nalawansha, Dhanusha A. ;

Li, Ke ;

Crews, Craig M. .

ACS CENTRAL SCIENCE, 2020, 6 (08) :1367-1375

[5] Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation [J].

Burslem, George M. ;

Schultz, Anna Reister ;

Bondeson, Daniel P. ;

Eide, Christopher A. ;

Stevens, Samantha L. Savage ;

Druker, Brian J. ;

Crews, Craig M. .

CANCER RESEARCH, 2019, 79 (18) :4744-4753

[6] 10 years into the resurgence of covalent drugs [J].

De Vita, Elena .

FUTURE MEDICINAL CHEMISTRY, 2021, 13 (02) :193-210

[7] Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations [J].

de Wispelaere, Melissanne ;

Du, Guangyan ;

Donovan, Katherine A. ;

Zhang, Tinghu ;

Eleuteri, Nicholas A. ;

Yuan, Jingting C. ;

Kalabathula, Joann ;

Nowak, Radoslaw P. ;

Fischer, Eric S. ;

Gray, Nathanael S. ;

Yang, Priscilla L. .

NATURE COMMUNICATIONS, 2019, 10 (1)

[8] Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry [J].

Dong, Jiajia ;

Krasnova, Larissa ;

Finn, M. G. ;

Sharpless, K. Barry .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2014, 53 (36) :9430-9448

[9] In Silico Modeling of PROTAC-Mediated Ternary Complexes: Validation and Application [J].

Drummond, Michael L. ;

Williams, Christopher I. .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2019, 59 (04) :1634-1644

[10] Proteolysis targeting chimeras (PROTACs) in 'beyond rule-of-five' chemical space: Recent progress and future challenges [J].

Edmondson, Scott D. ;

Yang, Bin ;

Fallan, Charlene .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (13) :1555-1564

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