Results 81 to 90 of about 11,335 (243)

PROTAC‑Mediated HMGCR Depletion Reprograms Lipid Metabolism in Breast Cancer to Potentiate Photoimmunotherapy via Ferroptosis. [PDF]

Adv Sci (Weinh)
This work introduces a study that identifies HMGCR as a novel target in TNBC and develops a light‐gated PROTAC nanomedicine. Upon irradiation, this agent selectively degrades HMGCR, reprogramming lipid metabolism to induce ferroptosis and potent antitumor immunity, thereby significantly enhancing photoimmunotherapy efficacy.
Su T, Li G, Guan Y, Tian Q, Qi Y, Zhang Y, Wei W, Duan X, Rui J, Zhu H, Lin Z, Xie C, Xu Z, Wu Y, Peng X, Wang Z, Chen K, Xin X, Zhang B.   +18 more
europepmc   +2 more sources

Smart Integration of Structural Biology and Medicinal Chemistry to Unlock Target‐Driven Drug Discovery

Medicinal Research Reviews, EarlyView.
ABSTRACT To enhance drug discovery efforts, medicinal chemists should evaluate, filter, and utilize relevant structural information about target proteins. Acquiring and interpreting protein structures is crucial for elucidating ligand‐receptor interactions and addressing ADME‐related considerations, making it an essential aspect of medicinal chemistry.
Matteo Rossi Sebastiano, Giulia Apprato, Serena Francisco, Giuseppe Ermondi, Giulia Caron   +4 more
wiley   +1 more source

Design and Synthesis of Polyamine‐Proteolysis Targeting Chimera Conjugates for Histone Deacetylase (HDAC) Degradation with Enhanced Cellular Uptake

ChemistryOpen, EarlyView.
In this article, proteolysis targeting chimeras (PROTACs) bearing a polyamine linker capable of crossing cancer cell membranes via the polyamine transport system are synthesized and evaluated. The results provide valuable insights for the design of PROTACs with enhanced cellular uptake efficiency.
Yanran Liu, Wentian Chen, Yanwei Shang, Chaonan Tang, Xianming Zeng, Jun Li, Wenting Du   +6 more
wiley   +1 more source

mRNA PROTACs: engineering PROTACs for high‐efficiency targeted protein degradation

MedComm
AbstractProteolysis‐targeting chimeras (PROTACs) are essential bifunctional molecules that target proteins of interest (POIs) for degradation by cellular ubiquitination machinery. Despite significant progress made in understanding PROTACs' functions, their therapeutic potential remains largely untapped.
Xiaoqi Xue, Chen Zhang, Xiaolin Li, Junqiao Wang, Haowei Zhang, Ying Feng, Naihan Xu, Hongyan Li, Chunyan Tan, Yuyang Jiang, Ying Tan   +10 more
openaire   +3 more sources

Disarming the Hsp70–Bim Alliance: Small‐Molecule and Peptidic Disruptors of a Chaperone‐Apoptotic Switch in Cancer

ChemistryOpen, EarlyView.
Targeting a nucleotide‐sensitive groove on Hsp70 that binds the Bim BH3 helix, we integrate structures, biophysics, and SAR from peptides, fragments, and phenalene‐dicarbonitrile “wedges.” These disrupt the Hsp70–Bim complex with sub‐µM cellular engagement and in vivo activity while sparing Hsp90/mortalin.
Emadeldin M. Kamel, Mohammed Al‐zharani, Lina M. Alneghery, Noha A. Ahmed, Faris F. Aba Alkhayl, Al Mokhtar Lamsabhi   +5 more
wiley   +1 more source

Nanomedicine Targeting Macrophage Immunometabolism in Atherosclerosis: Mechanisms and Therapeutic Prospects

Organ Medicine, EarlyView.
ABSTRACT Atherosclerosis, a chronic inflammatory–metabolic disorder, remains a leading cause of cardiovascular morbidity worldwide. This review explores the emerging paradigm of nanomedicine‐based targeting of macrophage immunometabolic reprogramming as a potentially transformative strategy for atherosclerosis treatment.
Zhenyu Liu, Wenfan Yang, Na Wang, Ya Wu
wiley   +1 more source

Application of PROTACs in target identification and validation

Acta Materia Medica
Proteolysis targeting chimeras (PROTACs), as a novel therapeutic drug model, has received widespread attention from academia and the pharmaceutical industry.
Yang Liu, Jing Liang, Rui Zhu, Yueying Yang, Yali Wang, Wenyi Wei, Hua Li, Lixia Chen   +7 more
doaj   +1 more source

Self-assembled Peptide-derived Proteolysis-targeting Chimera (PROTAC) Nanoparticles for Tumor-targeted and Durable PD-L1 Degradation in Cancer Immunotherapy.

Angewandte Chemie
Proteolysis-targeting chimeras (PROTACs) are a promising technique for the specific and durable degradation of cancer-related proteins via the ubiquitin-proteasome system in cancer treatment. However, the therapeutic efficacy of PROTACs is restricted due
Yujeong Moon, Hanhee Cho, Jinseong Kim, Sukyung Song, Jung Yeon Park, Jin Young Min, Eun Hee Han, Yongju Kim, Joon-Kyung Seong, M. Shim, Kwangmeyung Kim   +10 more
semanticscholar   +1 more source

AlphaFold2‐Guided Cyclic Peptide Stabilizer Design to Target Protein–Protein Interactions

Proteins: Structure, Function, and Bioinformatics, EarlyView.
ABSTRACT The control and modulation of protein–protein interactions (PPIs) is of central importance for the majority of biological processes and most biomedical applications. Stabilization of PPIs, besides inhibition, is of growing pharmaceutical interest.
Niklas Halbwedl, Martin Zacharias
wiley   +1 more source

MEGA PROTAC, MEGA DOCK-based PROTAC mediated ternary complex formation pipeline with sequential filtering and rank aggregation

Scientific Reports
Proteolysis-targeting chimaeras (PROTACs), which induce proteolysis by recruiting an E3 ligase to dock into a target protein, are acquiring popularity as a novel pharmacological modality because of the unique features of PROTAC, including high potency ...
Sadettin Y. Ugurlu, David McDonald, Ramazan Enisoglu, Zexuan Zhu, Shan He   +4 more
doaj   +1 more source