Chemistries of bifunctional PROTAC degraders DOI
Chao-Guo Cao,

Ming He,

Liguo Wang

et al.

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(16), P. 7066 - 7114

Published: Jan. 1, 2022

Proteolysis targeting chimeras (PROTACs) technology is a novel and promising therapeutic strategy using small molecules to induce ubiquitin-dependent degradation of proteins.

Language: Английский

Targeted protein degradation: expanding the toolbox DOI
Matthieu Schapira, Matthew F. Calabrese, Alex N. Bullock

et al.

Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(12), P. 949 - 963

Published: Oct. 30, 2019

Language: Английский

Citations

718
PROTACs: great opportunities for academia and industry DOI Creative Commons
Xiuyun Sun, Hongying Gao, Yiqing Yang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)

Published: Dec. 24, 2019

Although many kinds of therapies are applied in the clinic, drug-resistance is a major and unavoidable problem. Another disturbing statistic limited number drug targets, which presently only 20-25% all protein targets that currently being studied. Moreover, focus current explorations their enzymatic functions, ignores functions from scaffold moiety. As promising appealing technology, PROteolysis TArgeting Chimeras (PROTACs) have attracted great attention both academia industry for finding available approaches to solve above problems. PROTACs regulate function by degrading target proteins instead inhibiting them, providing more sensitivity drug-resistant greater chance affect nonenzymatic functions. been proven show better selectivity compared classic inhibitors. can be described as chemical knockdown approach with rapidity reversibility, presents new different biology other gene editing tools avoiding misinterpretations arise potential genetic compensation and/or spontaneous mutations. PRTOACs widely explored throughout world outperformed not cancer diseases, but also immune disorders, viral infections neurodegenerative diseases. present very powerful crossing hurdles discovery tool development biology, efforts needed gain get deeper insight into efficacy safety clinic. More binders E3 ligases applicable developing waiting exploration.

Language: Английский

Citations

513
Advancing targeted protein degradation for cancer therapy DOI
Brandon Dale, Meng Cheng, Kwang‐Su Park

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(10), P. 638 - 654

Published: June 15, 2021

Language: Английский

Citations

435
Development of targeted protein degradation therapeutics DOI
Philip P. Chamberlain, Lawrence G. Hamann

Nature Chemical Biology, Journal Year: 2019, Volume and Issue: 15(10), P. 937 - 944

Published: Sept. 16, 2019

Language: Английский

Citations

388
Targeting cell-cycle machinery in cancer DOI Creative Commons
Jan M. Suski, Marcin Braun, Vladislav Strmiska

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(6), P. 759 - 778

Published: April 22, 2021

Language: Английский

Citations

382
Protein degraders enter the clinic — a new approach to cancer therapy DOI

Deborah Chirnomas,

Keith R. Hornberger, Craig M. Crews

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(4), P. 265 - 278

Published: Feb. 13, 2023

Language: Английский

Citations

343
PROTACs: An Emerging Therapeutic Modality in Precision Medicine DOI Creative Commons

Dhanusha A. Nalawansha,

Craig M. Crews

Cell chemical biology, Journal Year: 2020, Volume and Issue: 27(8), P. 998 - 1014

Published: Aug. 1, 2020

Language: Английский

Citations

336
Targeting CDK4 and CDK6 in cancer DOI
Shom Goel, Johann S. Bergholz, Jean J. Zhao

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(6), P. 356 - 372

Published: March 18, 2022

Language: Английский

Citations

325
Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy DOI Creative Commons
Chi Zhang,

Ziling Zeng,

Dong Cui

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 18, 2021

Abstract Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way modulate protein homeostasis for therapy; however, the always-on bioactivity existing PROTACs potentially leads uncontrollable degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPN pro ) phototherapeutic activatable abilities photo-immunometabolic therapy. SPN can remotely generate singlet oxygen ( 1 O 2 under NIR photoirradiation eradicate tumor cells induce immunogenic cell death (ICD) enhance immunogenicity. Moreover, PROTAC function is specifically activated by biomarker (cathepsin B) trigger targeted proteolysis immunosuppressive indoleamine 2,3-dioxygenase (IDO) living mice. The persistent IDO blocks tryptophan (Trp)-catabolism program promotes activation effector T cells. Such SPNpro-mediated in-situ immunometabolic synergizes phototherapy boost antitumor T-cell immunity, effectively inhibiting growth metastasis. Thus, this study provides platform advance

Language: Английский

Citations

316
Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development DOI Creative Commons
Katherine A. Donovan, Fleur M. Ferguson, Jonathan W. Bushman

et al.

Cell, Journal Year: 2020, Volume and Issue: 183(6), P. 1714 - 1731.e10

Published: Dec. 1, 2020

Language: Английский

Citations

285