Results 1 to 10 of about 464,369 (258)

Targeted Protein Degradation [PDF]

JACS Au
Kira J. Weissman
europepmc   +5 more sources

Delivering Degradation: Nanomedicine and Programmable Proximity Platforms for Targeted Protein Degradation. [PDF]

Pharmaceutics
Targeted protein degradation (TPD) represents a whole new paradigm in cell-level therapeutic design, with its ability to remove target proteins, normally through the endogenous proteasomal, lysosomal, or autophagic systems, rather than the traditional ...
Amin A, Nawaz T, Oliveira Ferreira O, Santana de Oliveira M.   +3 more
europepmc   +2 more sources

Targeted Protein Degradation Strategies in DNA Virus Research. [PDF]

Viruses
DNA viruses rely extensively on host cellular machinery, including replication factors and transcriptional systems, to persist after infection. These mechanisms make studying and targeting DNA viral proteins challenging, as they also play key roles in ...
Lam M, Hill C, Thornburg E, DeSmet M.
europepmc   +2 more sources

A destination-driven framework for nanoparticle-enabled targeted protein degradation. [PDF]

Acta Pharm Sin B
Targeted protein degradation (TPD) offers a revolutionary paradigm to eliminate disease-driving proteins. Given the distinct technical requirements and challenges associated with degrading intracellular versus extracellular proteins, we classify existing
Wang Y, Xia X, Xie S, Tong F, Liu W, Gao H.   +5 more
europepmc   +2 more sources

Design principles for optogenetic-based targeted protein degradation. [PDF]

Synth Syst Biotechnol
Precise regulation of protein abundance is essential for understanding dynamic cellular processes and for advancing therapeutic development. However, existing approaches lack the spatiotemporal resolution required to these cellular processes.
Chen Y, Wang S, Xie L, Zhang L, Zhu M, Xu Y.   +5 more
europepmc   +2 more sources

Proteasome inhibition enhances lysosome-mediated targeted protein degradation. [PDF]

Cell Death Dis
Proteasome inhibitor drugs are currently used in the clinic to treat multiple myeloma and mantle cell lymphoma. These inhibitors cause accumulation of undegraded proteins, thus inducing proteotoxic stress and consequent cell death.
Elshazly AM, Hosseini N, Vangala J, Shen S, Neely V, Hu X, Pagare PP, Harada H, Grant S, Radhakrishnan SK.   +9 more
europepmc   +2 more sources

Targeted protein degradation: species, diseases and efficient utilization. [PDF]

J Transl Med
Background Targeted protein degradation (TPD) is a novel protein modulation strategy distinct from traditional inhibitors. Its core mechanism involves labeling proteins of interest to initiate endogenous protein clearance pathways, mainly including the ...
Yue T, He J, Hou J.
europepmc   +2 more sources

Targeted Protein Degradation of NUDT5 Dissociates Catalytic Inhibition from Protein Loss in 6-Thioguanine Response. [PDF]

Nat Commun
6-Thioguanine (6-TG) is an FDA-approved antimetabolite drug that is widely used clinically, including for the treatment of leukemia. Its cellular effects require metabolic activation and are regulated through interactions with various proteins such as ...
Marques AMC, Bauer LG, Nguyen TA, Orta AG, Venne JL, Cheng C, Balıkçı E, Liu Y, Tivon B, Kroupova A, Ciulli A, London N, Kubicek S, Huber KVM.   +13 more
europepmc   +2 more sources

Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2

Nature Communications, 2023
The Src homology 2 (SH2) domain recognizes phosphotyrosine (pY) post translational modifications in partner proteins to trigger downstream signaling. Drug discovery efforts targeting the SH2 domains have long been stymied by the poor drug-like properties
Sarath Ramachandran, Nikolai Makukhin, Kevin Haubrich, Manjula Nagala, Beth Forrester, Dylan M. Lynch, Ryan Casement, Andrea Testa, Elvira Bruno, Rosaria Gitto, Alessio Ciulli   +10 more
doaj   +1 more source

A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo

Nature Communications, 2022
Protein degraders are an emerging drug modality; however, their properties lie beyond typical drug-like space. Here the authors report optimisation via structure-based exit vector and linker design towards the VHL-recruiting PROTAC ACBI2, an orally ...
Christiane Kofink, Nicole Trainor, Barbara Mair, Simon Wöhrle, Melanie Wurm, Nikolai Mischerikow, Michael J. Roy, Gerd Bader, Peter Greb, Géraldine Garavel, Emelyne Diers, Ross McLennan, Claire Whitworth, Vesna Vetma, Klaus Rumpel, Maximilian Scharnweber, Julian E. Fuchs, Thomas Gerstberger, Yunhai Cui, Gabriela Gremel, Paolo Chetta, Stefan Hopf, Nicole Budano, Joerg Rinnenthal, Gerhard Gmaschitz, Moriz Mayer, Manfred Koegl, Alessio Ciulli, Harald Weinstabl, William Farnaby   +29 more
doaj   +1 more source