33893-36-6Relevant articles and documents
Modulators of hERAP2 discovered by high-throughput screening
Laura, Medve,Ronan, Gealageas,Vy, Lam Bao,Valentin, Guillaume,Omar, Castillo-Aguilera,Virgyl, Camberlein,Piveteau, Catherine,Melissa, Rosell,Charlotte, Fleau,Sandrine, Warenghem,Julie, Charton,Julie, Dumont-Ryckembusch,Damien, Bosc,Florence, Leroux,Peter, van Endert,Benoit, Deprez,Rebecca, Deprez-Poulain
, (2020/12/29)
Endoplasmic reticulum aminopeptidase 2, ERAP2, is an emerging pharmacological target in cancer immunotherapy and control of autoinflammatory diseases, as it is involved in antigen processing. It has been linked to the risk of development of spondyloarthritis, and it associates with the immune infiltration of tumours and strongly predicts the overall survival for patients receiving check-point inhibitor therapy. While some selective inhibitors of its homolog ERAP1 are available, no selective modulator of ERAP2 has been disclosed so far. In order to identify such compounds, we screened an in-house focused library of 1920 compounds designed to target metalloenzymes. Structure-Activity Relationships and docking around two hits led to the discovery of selective inhibitors of ERAP2. Amid those, some bind to yet untapped amino-acids in the S1 pocket. Importantly, we disclose also the first activator of small substrates hydrolysis by ERAP2. Inhibitors and activators identified in this study could serve as useful starting points for optimization.
The effect of various zinc binding groups on inhibition of histone deacetylases 1-11
Madsen, Andreas S.,Kristensen, Helle M. E.,Lanz, Gyrithe,Olsen, Christian A.
, p. 614 - 626 (2014/03/21)
Histone deacetylases (HDACs) have the ability to cleave the acetyl groups of ε-N-acetylated lysine residues in a variety of proteins. Given that human cells contain thousands of different acetylated lysine residues, HDACS may regulate a wide variety of processes including some implicated in conditions such as cancer and neurodegenerative disorders. Herein we report the synthesis and ina vitro biochemical profiling of a series of compounds, including known inhibitors as well as novel chemotypes, that incorporate putative new zinc binding domains. By evaluating the compound collection against all 11 recombinant human HDACs, we found that the trifluoromethyl ketone functionality provides potent inhibition of all four subclasses of the Zn2+- dependent HDACs. Potent inhibition was observed with two different scaffolds, demonstrating the efficiency of the trifluoromethyl ketone moiety as a zinc binding motif. Interestingly, we also identified silanediol as a zinc binding group with potential for future development of non-hydroxamate classa I and classa IIb HDAC inhibitors.
A practical and efficient method for the preparation of sulfonamides utilizing Cl3CCN/PPh3
Chantarasriwong, Oraphin,Jang, Doo Ok,Chavasiri, Warinthorn
, p. 7489 - 7492 (2007/10/03)
Cl3CCN in combination with PPh3 proved to be a highly reactive reagent for the conversion of sulfonic acids to the corresponding sulfonyl chlorides in refluxing CH2Cl2. Upon reaction with amines, the corresponding sulfonamides were obtained in good to excellent yields.
