Emerging degrader technologies engaging lysosomal pathways
Targeted protein degradation (TPD) provides unprecedented opportunities for drug
discovery. While the proteolysis-targeting chimera (PROTAC) technology has already …
discovery. While the proteolysis-targeting chimera (PROTAC) technology has already …
[HTML][HTML] Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches
Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due
to their role in disease, notably cancer. Since their discovery, several mechanisms of RTK …
to their role in disease, notably cancer. Since their discovery, several mechanisms of RTK …
Proteome integral solubility alteration: a high-throughput proteomics assay for target deconvolution
Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the
physicochemical properties of proteins in cell lysates, living cells, and organisms. These …
physicochemical properties of proteins in cell lysates, living cells, and organisms. These …
CETSA and thermal proteome profiling strategies for target identification and drug discovery of natural products
Y Tu, L Tan, H Tao, Y Li, H Liu - Phytomedicine, 2023 - Elsevier
Background Monitoring target engagement at various stages of drug development is
essential for natural product (NP)-based drug discovery and development. The cellular …
essential for natural product (NP)-based drug discovery and development. The cellular …
[HTML][HTML] Covalent inhibition of NSD1 histone methyltransferase
The nuclear receptor-binding SET domain (NSD) family of histone methyltransferases is
associated with various malignancies, including aggressive acute leukemia with NUP98 …
associated with various malignancies, including aggressive acute leukemia with NUP98 …
[HTML][HTML] Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3
J Böttcher, D Dilworth, U Reiser, RA Neumüller… - Nature chemical …, 2019 - nature.com
Here, we report the fragment-based discovery of BI-9321, a potent, selective and cellular
active antagonist of the NSD3-PWWP1 domain. The human NSD3 protein is encoded by the …
active antagonist of the NSD3-PWWP1 domain. The human NSD3 protein is encoded by the …
Mechanistic and structural features of PROTAC ternary complexes
R Casement, A Bond, C Craigon, A Ciulli - Targeted protein degradation …, 2021 - Springer
The rapid and ever-growing advancements from within the field of proteolysis-targeting
chimeras (PROTAC)-induced protein degradation have driven considerable development to …
chimeras (PROTAC)-induced protein degradation have driven considerable development to …
Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2
S Ramachandran, N Makukhin, K Haubrich… - Nature …, 2023 - nature.com
Abstract The Src homology 2 (SH2) domain recognizes phosphotyrosine (pY) post
translational modifications in partner proteins to trigger downstream signaling. Drug …
translational modifications in partner proteins to trigger downstream signaling. Drug …
Validating small molecule chemical probes for biological discovery
V Vu, MM Szewczyk, DY Nie… - Annual review of …, 2022 - annualreviews.org
Small molecule chemical probes are valuable tools for interrogating protein biological
functions and relevance as a therapeutic target. Rigorous validation of chemical probe …
functions and relevance as a therapeutic target. Rigorous validation of chemical probe …
Isothermal chemical denaturation assay for monitoring protein stability and inhibitor interactions
R Mahran, N Vello, A Komulainen, M Malakoutikhah… - Scientific Reports, 2023 - nature.com
Thermal shift assay (TSA) with altered temperature has been the most widely used method
for monitoring protein stability for drug research. However, there is a pressing need for …
for monitoring protein stability for drug research. However, there is a pressing need for …