Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs.
Shanique B. Alabi,Craig M. Crews +1 more
TLDR
Targeted protein degradation (TPD) as discussed by the authors is a novel and innovative chemical tool and therapeutic modality that facilitates complete removal of the protein molecules from within or outside the cell.About:
This article is published in Journal of Biological Chemistry.The article was published on 2021-01-01 and is currently open access. It has received 81 citations till now. The article focuses on the topics: Protein degradation & Proteolysis targeting chimera.read more
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PROTAC targeted protein degraders: the past is prologue
TL;DR: Targeted protein degradation with proteolysis-targeting chimeras (PROTACs) has the potential to tackle disease-causing proteins that have historically been highly challenging to target with conventional small molecules as mentioned in this paper .
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Small molecules and their impact in drug discovery: a perspective on the occasion of the 125th anniversary of the Bayer Chemical Research Laboratory.
TL;DR: The year 2021 marks the 125th anniversary of the Bayer Chemical Research Laboratory in Wuppertal, Germany and a significant number of prominent small-molecule drugs, from Aspirin to Xarelto, have emerged from this research site as mentioned in this paper .
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A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo
Christiane C. Kofink,Nicole Trainor,Barbara Mair,Simon Wöhrle,Melanie Wurm,Nikolai Mischerikow,Michael J. Roy,Gerd Bader,Peter Greb,Geraldine Garavel,Emelyne Diers,Ross Sinclair McLennan,Claire Whitworth,Vesna Vetma,Klaus Rumpel,Maximilian Scharnweber,Julian E. Fuchs,Thomas Gerstberger,Yunhai Cui,Gabriela Gremel,Paolo Chetta,S Hopf,Nicole Budano,Joerg Rinnenthal,Gerhard Gmaschitz,M. Mayer,Manfred Koegl,Alessio Ciulli,Harald Weinstabl,William Farnaby +29 more
TL;DR: In this article , the BAF Chromatin Remodelling complex ATPase SMARCA2 over its closely related paralogue SMAR CA4 was used to evaluate in vivo the synthetic lethality concept of the dependency of the two proteins.
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Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.
TL;DR: A comprehensive review of small-molecule ubiquitin-proteasome (UPS) inhibitors can be found in this paper, where the authors highlight advancements in the development of targeted protein degradation strategies for cancer therapeutics.
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Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands.
Hong-Yi Zhao,Hai-peng Wang,Yuqian Bao,Hao Zhang,Minhang Xin,Xiao-Xiao Xi,Hao Lei,Shuai Mao,Dong-Hui Li,San-Qi Zhang +9 more
TL;DR: Covalent PROTAC CP17, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFRL858R/T790M and EGFRdel19, reaching the lowest DC50 values among all reported EGFR-targeting PROTACs.
References
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Journal ArticleDOI
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
Tissue-based map of the human proteome
Mathias Uhlén,Mathias Uhlén,Linn Fagerberg,Björn M. Hallström,Cecilia Lindskog,Per Oksvold,Adil Mardinoglu,Åsa Sivertsson,Caroline Kampf,Evelina Sjöstedt,Evelina Sjöstedt,Anna Asplund,IngMarie Olsson,Karolina Edlund,Emma Lundberg,Sanjay Navani,Cristina Al-Khalili Szigyarto,Jacob Odeberg,Dijana Djureinovic,Jenny Ottosson Takanen,Sophia Hober,Tove Alm,Per-Henrik Edqvist,Holger Berling,Hanna Tegel,Jan Mulder,Johan Rockberg,Peter Nilsson,Jochen M. Schwenk,Marica Hamsten,Kalle von Feilitzen,Mattias Forsberg,Lukas Persson,Fredric Johansson,Martin Zwahlen,Gunnar von Heijne,Jens Nielsen,Jens Nielsen,Fredrik Pontén +38 more
TL;DR: In this paper, a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level.
Journal ArticleDOI
The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
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In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.
Lyubomir T. Vassilev,Binh Thanh Vu,Bradford Graves,Daisy Carvajal,Frank John Podlaski,Zoran Filipovic,Norman Kong,Ursula Kammlott,Christine Lukacs,Christian Klein,Nader Fotouhi,Liu Emily Aijun +11 more
TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.
Journal ArticleDOI
The Ubiquitin Code
David Komander,Michael Rape +1 more
TL;DR: The structure, assembly, and function of the posttranslational modification with ubiquitin, a process referred to as ubiquitylation, controls almost every process in cells.