Eliminating Aggressive Cancers via PROTAC-like Inducers of Ferroptosis DOI Open Access
Avital Oknin-Vaisman, Deepanjan Panda, Rostislav Novak

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 29, 2024

Abstract Aggressive and therapy-resistant cancers present a significant challenge to treatment are associated with poor patients’ survival. Identifying molecular pathways compounds that target these is critical for improving patient outcomes. RNF4, an E3-ubiquitin ligase, pivotal in oncoprotein stabilization DNA repair, enhancing cancer cell survival driving tumorigenesis. Elevated RNF4 levels prognosis patients. Here, we describe the development of R4VPs, proteolysis-targeted chimeras-like (PROTACs-like). R4VPs promote degradation reduce its stabilized oncoproteins. Notably, induce ferroptotic death selectively cells, sparing non-tumorigenic primary cells. Surprisingly, R4VPs-induced ferroptosis independent but preferentially targets tumor-driving mutations, particularly those EGFR pathway, while not affecting PI3K-transformed effectively melanoma sarcomas including patient-derived sarcoma tumor Our findings highlight potential inducers such as therapeutic strategy therapy resistance, aggressive, hard-to-treat cancers. Teaser cells non-transomed

Language: Английский

Discovery of the First Potent ROR1 Degrader for the Treatment of Non-Small Cell Lung Cancer DOI
Jinlin Li,

Lin Li,

Hou Cai-yun

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117325 - 117325

Published: Jan. 1, 2025

Language: Английский

Citations

1
Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions DOI Creative Commons
Rajamanikkam Kamaraj, Subhrojyoti Ghosh,

Souvadra Das

et al.

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: 35(8), P. 1089 - 1115

Published: July 11, 2024

Targeted protein degradation or TPD, is rapidly emerging as a treatment that utilizes small molecules to degrade proteins cause diseases. TPD allows for the selective removal of disease-causing proteins, including proteasome-mediated degradation, lysosome-mediated and autophagy-mediated degradation. This approach has shown great promise in preclinical studies now being translated treat numerous diseases, neurodegenerative infectious cancer. review discusses latest advances its potential new chemical modality immunotherapy, with special focus on innovative applications cutting-edge research PROTACs (Proteolysis TArgeting Chimeras) their efficient translation from scientific discovery technological achievements. Our also addresses significant obstacles prospects this domain, while offering insights into future immunotherapeutic applications.

Language: Английский

Citations

6
Degrading Mutant IDH1 Employing a PROTAC-Based Approach Impairs STAT3 Activation DOI

Hashnu Dutta,

Nishant Jain

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110281 - 110281

Published: Jan. 1, 2025

Language: Английский

Citations

0
Light-Activatable Photochemically Targeting Chimeras (PHOTACs) Enable the Optical Control of Targeted Protein Degradation of HDAC6 DOI
Silas Wurnig,

Maria Hanl,

Thomas Geiger

et al.

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The first light-activatable photochemically targeting chimeras (PHOTACs) designed for the targeted degradation of histone deacetylase 6 are reported.

Language: Английский

Citations

0
Discovery of the First Potent Ror1 Degrader for the Treatment of Non-Small Cell Lung Cancer DOI
Fengtao Zhou, Jinlin Li,

Lin Li

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0
Targeted protein degradation: expanding the technology to facilitate the clearance of neurotoxic proteins in neurodegenerative diseases DOI
Xin Wang,

Shuai Wen,

Panpan Yang

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102584 - 102584

Published: Nov. 1, 2024

Language: Английский

Citations

0
Eliminating Aggressive Cancers via PROTAC-like Inducers of Ferroptosis DOI Open Access
Avital Oknin-Vaisman, Deepanjan Panda, Rostislav Novak

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 29, 2024

Abstract Aggressive and therapy-resistant cancers present a significant challenge to treatment are associated with poor patients’ survival. Identifying molecular pathways compounds that target these is critical for improving patient outcomes. RNF4, an E3-ubiquitin ligase, pivotal in oncoprotein stabilization DNA repair, enhancing cancer cell survival driving tumorigenesis. Elevated RNF4 levels prognosis patients. Here, we describe the development of R4VPs, proteolysis-targeted chimeras-like (PROTACs-like). R4VPs promote degradation reduce its stabilized oncoproteins. Notably, induce ferroptotic death selectively cells, sparing non-tumorigenic primary cells. Surprisingly, R4VPs-induced ferroptosis independent but preferentially targets tumor-driving mutations, particularly those EGFR pathway, while not affecting PI3K-transformed effectively melanoma sarcomas including patient-derived sarcoma tumor Our findings highlight potential inducers such as therapeutic strategy therapy resistance, aggressive, hard-to-treat cancers. Teaser cells non-transomed

Language: Английский

Citations

0