Structural highlights
Function
CATS_HUMAN Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N.
Publication Abstract from PubMed
Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.
Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors.,Schade M, Merla B, Lesch B, Wagener M, Timmermanns S, Pletinckx K, Hertrampf T J Med Chem. 2020 Oct 22;63(20):11801-11808. doi: 10.1021/acs.jmedchem.0c00949. , Epub 2020 Sep 17. PMID:32880457[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schade M, Merla B, Lesch B, Wagener M, Timmermanns S, Pletinckx K, Hertrampf T. Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors. J Med Chem. 2020 Oct 22;63(20):11801-11808. doi: 10.1021/acs.jmedchem.0c00949. , Epub 2020 Sep 17. PMID:32880457 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c00949
