PROTACs: past, present and future

K Li, CM Crews - Chemical Society Reviews, 2022 - pubs.rsc.org
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules consisting of
one ligand that binds to a protein of interest (POI) and another that can recruit an E3 …

[HTML][HTML] PROTAC targeted protein degraders: the past is prologue

M Békés, DR Langley, CM Crews - Nature Reviews Drug Discovery, 2022 - nature.com
Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to
tackle disease-causing proteins that have historically been highly challenging to target with …

[HTML][HTML] KRAS mutation: from undruggable to druggable in cancer

L Huang, Z Guo, F Wang, L Fu - Signal transduction and targeted …, 2021 - nature.com
Cancer is the leading cause of death worldwide, and its treatment and outcomes have been
dramatically revolutionised by targeted therapies. As the most frequently mutated oncogene …

Advancing targeted protein degradation for cancer therapy

B Dale, M Cheng, KS Park, HÜ Kaniskan… - Nature Reviews …, 2021 - nature.com
The human proteome contains approximately 20,000 proteins, and it is estimated that more
than 600 of them are functionally important for various types of cancers, including nearly 400 …

[HTML][HTML] Proteolysis-targeting chimeras (PROTACs) in cancer therapy

X Li, W Pu, Q Zheng, M Ai, S Chen, Y Peng - Molecular cancer, 2022 - Springer
Proteolysis-targeting chimeras (PROTACs) are engineered techniques for targeted protein
degradation. A bifunctional PROTAC molecule with two covalently-linked ligands recruits …

[HTML][HTML] Targeting STAT3 in cancer immunotherapy

S Zou, Q Tong, B Liu, W Huang, Y Tian, X Fu - Molecular cancer, 2020 - Springer
As a point of convergence for numerous oncogenic signaling pathways, signal transducer
and activator of transcription 3 (STAT3) is central in regulating the anti-tumor immune …

Advances in targeting 'undruggable'transcription factors with small molecules

MJ Henley, AN Koehler - Nature Reviews Drug Discovery, 2021 - nature.com
Transcription factors (TFs) represent key biological players in diseases including cancer,
autoimmunity, diabetes and cardiovascular disease. However, outside nuclear receptors …

[HTML][HTML] Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders

CJ Diehl, A Ciulli - Chemical Society Reviews, 2022 - pubs.rsc.org
The von Hippel-Lindau (VHL) Cullin RING E3 ligase is an essential enzyme in the ubiquitin-
proteasome system that recruits substrates such as the hypoxia inducible factor for …

Development of antibody-based PROTACs for the degradation of the cell-surface immune checkpoint protein PD-L1

AD Cotton, DP Nguyen, JA Gramespacher… - Journal of the …, 2021 - ACS Publications
Targeted protein degradation has emerged as a new paradigm to manipulate cellular
proteostasis. Proteolysis-targeting chimeras (PROTACs) are bifunctional small molecules …

Targeted protein degradation: expanding the toolbox

M Schapira, MF Calabrese, AN Bullock… - Nature reviews Drug …, 2019 - nature.com
Proteolysis-targeting chimeras (PROTACs) and related molecules that induce targeted
protein degradation by the ubiquitin–proteasome system represent a new therapeutic …