Small molecule inhibitors targeting the cancers DOI Creative Commons
Guihong Liu, Tao Chen, Xin Zhang

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 13, 2022

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary therapies for cancer. Due to their advantages a wide range targets, convenient medication, ability penetrate into central nervous system, many efforts have been devoted developing more small inhibitors. To date, 88 approved by United States Food Drug Administration treat cancers. Despite remarkable progress, cancer treatment still face obstacles, such as low response rate, short duration response, toxicity, biomarkers, resistance. better promote development targeting cancers, we comprehensively reviewed involved all agents pivotal drug candidates clinical trials arranged signaling pathways classification We discussed lessons learned from these agents, proper strategies overcome resistance arising different mechanisms, combination concerned Through our review, hoped provide insights perspectives research treatment.

Language: Английский

E3 ligases and deubiquitinating enzymes regulating the MAPK signaling pathway in cancers DOI
Hong‐Beom Park, Kwang‐Hyun Baek

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1877(3), P. 188736 - 188736

Published: May 1, 2022

Language: Английский

Citations

101
Targeted protein degradation: from mechanisms to clinic DOI
Jonathan M. Tsai, Radosław P. Nowak, Benjamin L. Ebert

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(9), P. 740 - 757

Published: April 29, 2024

Language: Английский

Citations

101
Radiotherapy-Triggered Proteolysis Targeting Chimera Prodrug Activation in Tumors DOI
Chunrong Yang, Yuchen Yang, Yujie Li

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 145(1), P. 385 - 391

Published: Dec. 21, 2022

Proteolysis targeting chimera (PROTAC) is an emerging protein degradation strategy, which shows excellent advantages in those so-called "undruggable" proteins. However, the potential systemic toxicity of PROTACs caused by undesired off-tissue may limit application clinical practice. Here we reported a radiotherapy-triggered PROTAC prodrug (RT-PROTAC) activation strategy to precisely and spatiotemporally control through X-ray radiation. We demonstrated this concept incorporating inducible phenyl azide-cage bromodomain (BRD)-targeting form first RT-PROTAC. The RT-PROTAC exhibits little activity but can be activated radiation vitro vivo. Activated degrades BRD4 BRD2 with comparable effect degrader synergistic antitumor potency radiotherapy MCF-7 xenograft model. Our work provides alternative vivo points avenue for reducing PROTACs.

Language: Английский

Citations

96
Small-molecule discovery through DNA-encoded libraries DOI
Alexander A. Peterson, David R. Liu

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(9), P. 699 - 722

Published: June 16, 2023

Language: Английский

Citations

96
Small molecule inhibitors targeting the cancers DOI Creative Commons
Guihong Liu, Tao Chen, Xin Zhang

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 13, 2022

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary therapies for cancer. Due to their advantages a wide range targets, convenient medication, ability penetrate into central nervous system, many efforts have been devoted developing more small inhibitors. To date, 88 approved by United States Food Drug Administration treat cancers. Despite remarkable progress, cancer treatment still face obstacles, such as low response rate, short duration response, toxicity, biomarkers, resistance. better promote development targeting cancers, we comprehensively reviewed involved all agents pivotal drug candidates clinical trials arranged signaling pathways classification We discussed lessons learned from these agents, proper strategies overcome resistance arising different mechanisms, combination concerned Through our review, hoped provide insights perspectives research treatment.

Language: Английский

Citations

91