Results 71 to 80 of about 823,777 (226)

Opportunities and challenges of PROTAC in the treatment of protein-driven diseases

Results in Chemistry
Targeted protein degradation (TPD) has transformed the landscape of drug discovery by exploiting the ubiquitin-proteasome system (UPS) to eliminate, rather than inhibit, pathogenic proteins.
Zhe Zhou, Peng Liu, Yang Li, Xuelian Liu, Jinyao Li   +4 more
doaj   +1 more source

Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy

Journal of Hematology & Oncology, 2021
Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme that catalyzes the oxidation of L-tryptophan. Functionally, IDO1 has played a pivotal role in cancer immune escape via catalyzing the initial step of the kynurenine pathway, and overexpression of IDO1
Kai Tang, Ya-Hong Wu, Yihui Song, Bin Yu
doaj   +1 more source

Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation

Advanced Science, EarlyView.
Dynamic supramolecular assembly reshapes targeted protein degradation by coordinating modular degrader construction, delivery, functional integration, and intracellular assembly or activation across proteasomal, endosomal–lysosomal, and autophagy–lysosomal pathways.
Kongjun Liu, Xue Yuan, Yan Zhou, Rui Yuan, Shaocheng Xie, Yong Chen, Peiyi Wang, Jianmei Gao, Qihai Gong   +8 more
wiley   +1 more source

Design, synthesis, and biological characterization of proteolysis targeting chimera (PROTACs) for the Ataxia telangiectasia and RAD3-related (ATR) kinase [PDF]

The Ataxia telangiectasia and RAD3-related (ATR) kinase is a key regulator of DNA replication stress responses and DNA-damage checkpoints. Several potent and selective ATR inhibitors are reported and four of them are currently in clinical trials in ...
Anne-Christin, Sarnow, Abdallah M. , Alfayomy, Ramy, Ashry, Matthias, Schmidt, Oliver H., Krämer, Frank, Erdmann, Anita, Kansy, Wolfgang, Sippl   +7 more
core   +2 more sources

Proteolysis Targeting Chimeras (PROTACs) in Breast Cancer Therapy

ChemMedChem
AbstractBreast cancer (BC) accounts for 30 % of cancer cases among women cancer patients globally, indicating the urgent need for the development of selective therapies targeting BCs. Recently, proteolysis‐targeting chimera (PROTAC) has emerged as a promising strategy to target breast cancer. PROTAC is a chimeric molecule consisting of a target protein
Yerim Jin, Yeongju Lee
openaire   +2 more sources

Multi‐Technique Integration Identifies O‐GlcNAc Transferase in Fibroblast‐Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis

Advanced Science, EarlyView.
AI‑guided single‑cell transcriptomics identifies OGT as a key regulator enriched in rheumatoid arthritis fibroblast‑like synoviocytes (RA‐FLSs). Inflammatory stimuli activate the OGT–SAP130 axis, which modulates the H3K27ac/H3K27me3 balance and epigenetically silences BTG2, promoting aggressive transformation of RA‑FLSs.
Duoli Xie, Jie Huang, Chunhao Cao, Zhenchao Tang, Xingchen Li, Jianmin Guo, Xinxin Chen, Fang Wang, Dongyi He, Jie Li, Yu Du, Bing He, Jianhua Yao, Aiping Lu, Chao Liang   +14 more
wiley   +1 more source

Enhancing Antiproliferative Activity and Selectivity of a FLT‑3 Inhibitor by Proteolysis Targeting Chimera Conversion

, 2018
The receptor tyrosine kinase FLT-3 is frequently mutated in acute myeloid leukemia; however, current small molecule inhibitors suffer from limited efficacy in the clinic. Conversion of a FLT-3 inhibitor (quizartinib) into a proteolysis targeting chimera (
Jayoung Song (758681), Craig M. Crews (135604), John Hines (135601), Xin Chen (14149), George M. Burslem (5987708)   +4 more
core   +2 more sources

Design and development of PROTACs: A new paradigm in anticancer drug discovery

Medicine in Drug Discovery
PROTAC (Proteolysis targeting chimera) is a potential revolutionary strategy in cancer drug development focusing on their ability to target specific receptors like androgen and BRD4, which are vital for the progression and development of several cancers.
Vishal Mathur, Mukund Jha, Iqra Zai, Moksh Mahajan, Shagufi Nazar, Shaheen Ali, Anam Ilyas, Sana Tanweer, Javed Ali, Ozair Alam   +9 more
doaj   +1 more source

Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4‐Dependent Enhancer Activation

Advanced Science, EarlyView.
To model a nutrient‐restricted tumor microenvironment, breast cancer cells were adapted to low glucose and glutamine levels. In the adapted cells, BRD4‐driven enhancer activation increases pro‐invasive EDN1 expression, facilitated by ATF3/c‐JUN and reinforced by enhancer RNA.
Poshan Yugal Bhattarai, Arathy Vasukutty, Yujin Na, Sung‐Chul Lim, Hong Seok Choi   +4 more
wiley   +1 more source

Site‐Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids

Angewandte Chemie, EarlyView.
Genetic code expansion (GCE) enables site‐specific installation of noncanonical amino acids containing bioorthogonal conjugation handles, allowing precise, homogeneous protein modification. This review examines the principles of orthogonal translation, surveys the chemistries available for chemoselective labeling, and highlights emerging multi‐site ...
Rahul Sarkar, Manas Joshi, Abhishek Chatterjee   +2 more
wiley   +2 more sources