- 1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors.
1,2,6-Thiadiazinones as Novel Narrow Spectrum Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) Inhibitors.
Molecules (Basel, Switzerland) (2018-05-23)
Christopher R M Asquith, Paulo H Godoi, Rafael M Couñago, Tuomo Laitinen, John W Scott, Christopher G Langendorf, Jonathan S Oakhill, David H Drewry, William J Zuercher, Panayiotis A Koutentis, Timothy M Willson, Andreas S Kalogirou
PMID29783765
RÉSUMÉ
We demonstrate for the first time that 4H-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors.
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Millipore
Protease Inhibitor Cocktail Set VII, Protease Inhibitor Cocktail Set VII contains five protease inhibitors with broad specificity. Recommended for purification of proteins containing His•Tag sequences.