Results 241 to 250 of about 14,786 (290)

The aptamer-based RNA-PROTAC

Bioorganic & Medicinal Chemistry, 2023
RNA-binding proteins (RBPs) dysfunction has been implicated in a number of diseases, and RBPs have traditionally been considered to be undruggable targets. Here, targeted degradation of RBPs is achieved based on the aptamer-based RNA-PROTAC, which consists of a genetically encoded RNA scaffold and a synthetic heterobifunctional molecule.
Yan Xu, Yi Yuan, Ding-Qiang Fu, Yi Fu, Shan Zhou, Wan-Ting Yang, Xu-Yang Wang, Guang-Xun Li, Juan Dong, Feng Du, Xin Huang, Qi-Wei Wang, Zhuo Tang   +12 more
openaire   +2 more sources

Targeted Degradation of ZBP1 with Covalent PROTACs for Anti-Inflammatory Treatment of Infections.

Angewandte Chemie
Z-DNA binding protein 1 (ZBP1) has emerged as a critical pathogen-sensing protein that, upon activation, triggers necroptotic signaling cascades, leading to a potent inflammatory response and potentially causing significant tissue damage.
Rentang Huang, Yusi Hu, Yi-Fan Wang, Shiyu Zhang, Zhi-Gang Wang, Dai-Wen Pang, Shu-Lin Liu   +6 more
semanticscholar   +1 more source

Evaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.

Journal of Medicinal Chemistry
PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration.
Marisa Actis, Joel O Cresser-Brown, Elizabeth A. Caine, Martin Steger, Anup Aggarwal, Anand Mayasundari, Nancy Murphy, G. Valinciute, Yong Li, Xiang Fu, Lei Yang, Graham P. Marsh, Gareth Hughes, Burhan Karadogan, Dean Wheeler, Mark C. Norley, Freya Spain, M. Urh, M. Roussel, B. Schwalb, Henrik Daub, Kristin M Riching, Hannah J Maple, Gisele Nishiguchi, Zoran Rankovic   +24 more
semanticscholar   +1 more source

Beyond Rule of Five and PROTACs in Modern Drug Discovery: Polarity Reducers, Chameleonicity, and the Evolving Physicochemical Landscape.

Journal of Medicinal Chemistry
Developing orally bioavailable drugs demands an understanding of absorption in early drug development. Traditional methods and physicochemical properties optimize absorption for rule of five (Ro5) compounds; beyond rule of five (bRo5) drugs necessitate ...
Edward Price, Manuel Weinheimer, Alexey Rivkin, Gary Jenkins, Marjoleen Nijsen, Philip B Cox, D. Degoey   +6 more
semanticscholar   +1 more source

PROTAC antibiotics: the time is now

Expert Opinion on Drug Discovery, 2023
Novel antibiotics are needed to keep antibiotic resistance at bay and to improve treatment of the many drug-susceptible infections for which current therapies achieve poor cure rates. While revolutionizing human therapeutics, the concept of targeted protein degradation (TPD) by bifunctional proteolysis targeting chimeras (PROTACs) has not yet been ...
Jickky Palmae Sarathy, Courtney C. Aldrich, Mei-Lin Go, Thomas Dick   +3 more
openaire   +2 more sources

Structural and Physicochemical Features of Oral PROTACs.

Journal of Medicinal Chemistry
Achieving oral bioavailability with Proteolysis Targeting Chimeras (PROTACs) is a key challenge. Here, we report the in vivo pharmacokinetic properties in mouse, rat, and dog of four clinical oral PROTACs and compare with an internally derived data set ...
Markus Schade, James S Scott, Thomas G Hayhow, A. Pike, I. Terstiege, Marie Ahlqvist, Johan R Johansson, Coura Diène, Charlene Fallan, Amber Y. S. Balazs, Elisabetta Chiarparin, David M Wilson   +11 more
semanticscholar   +1 more source

Targeted Degradation of Proteins by PROTACs

Current Protocols in Chemical Biology, 2010
AbstractIn recent years, small interference RNAs (siRNAs) have greatly enhanced our understanding of protein functions by allowing knockdown of targeted proteins at the mRNA level. Similarly, in an effort to achieve degradation of targeted proteins at the post‐translational level, chimeric small molecules called “PROTACs” (PROteolysis TArgeting ...
Eun Ryoung, Jang, Wooin, Lee, Kyung Bo, Kim   +2 more
openaire   +2 more sources

Advancing Design Strategy of PROTACs for Cancer Therapy

MedComm
Proteolysis targeting chimeras (PROTACs) have emerged as a groundbreaking class of anticancer therapeutics. These bifunctional molecules harness the endogenous ubiquitin–proteasome system to facilitate the degradation of targeted proteins of interest ...
Hang Luo, Yuan Tian, Razack Abdullah, Baoting Zhang, Yuan Ma, Ge Zhang   +5 more
semanticscholar   +1 more source

Bifunctional Molecules beyond PROTACs

Journal of Medicinal Chemistry, 2020
Heterobifunctional molecules, which recruit E3 ligases to ubiquitinate a target protein of interest, have found wide application as both biological tools and molecules with the potential to have clinical effects. In their recent paper, Yamazoe et al. report a heterobifunctional molecule that recruits the phosphatase PP1 to promote the dephosphorylation
openaire   +2 more sources

Prodrug Strategy for PROTACs: High Efficiency and Low Toxicity

ACS Omega
At present, PROTACs have garnered significant attention as a burgeoning therapeutic approach. Relying on endogenous E3 ubiquitin ligases, PROTACs achieve the catalytic degradation of target proteins through a cyclic catalytic mechanism.
Yuqin Li, Yongcheng Guo, Siming Ma, Baobang Long, Rui Kong, Xin Huang, Kun Zhao, Ying Zhi   +7 more
semanticscholar   +1 more source