Excited to share our latest paper out in Angewandte:
Using a phenomics-based screen, we uncovered that CHKA (choline kinase α) - a key metabolic enzyme in cancer/immune signalling - is an off-target of well-known G9a/GLP inhibitors (UNC0638/UNC0737).
📎 Paper: Phenomics-Based Discovery of Novel Orthosteric Choline Kinase Inhibitors (Angew. Chem. Int. Ed., DOI:10.1002/anie.202420149)
🔍 How do you assess selectivity for #covalent inhibitors? Our latest study just out in The Journal of Medicinal Chemistry reveals fascinating insights. 👇
Dual pharmacology: Covalent inhibitors can unexpectedly interact with target proteins via non-covalent interactions. In our study, we explore this phenomenon using biochemical, biophysical, and cell target engagement assays.
Case Study: The FDA-approved #BTK inhibitor #ibrutinib surprised us! It not only targets kinases but also binds and inhibits two non-kinase proteins: NUDT5 and NUDT14. 🎯
Warhead Independence: Interestingly, these effects are independent of the reactive acrylamide warhead. Mass spectrometry and protein crystallography confirm this unexpected behavior. 💡
New scaffold to explore ADP-ribose metabolism: By performing SAR studies, we identify a first-in-class, non-covalent dual inhibitor for NUDT5 and NUDT14. 🌟
📖 Read the full story here: https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c00072
We are looking for two enthusiastic postdoctoral fellows with expertise in structural biology to join us in our effort to study the function of proteins involved in #ubiquitination & #RNAmetabolism - please check out the links below for more information and apply online!
Job Details (corehr.com) – closing date: 09-Oct-2023 12:00
Job Details (corehr.com) – closing date: 09-Oct-2023 12:00
