Structural highlights
Function
STK25_HUMAN Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration.[1]
Publication Abstract from PubMed
We describe the synthesis of a series of 3-t-butyl 5-aminopyrazole p-substituted arylamides as inhibitors of serine-threonine25 (STK25), an enzyme implicated in the progression of non-alcoholic fatty liver disease (NAFLD). Appending a p-N-pyrrolidinosulphonamide group to the arylamide group led to a 'first-in kind' inhibitor with IC50 = 228 nM. A co-crystal structure with STK 25 revealed productive interactions which were also reproduced using molecular docking. A new series of triazolo dihydro oxazine carboxamides of 3-t-butyl 5-aminopyrazole was not active against STK25.
Targeting non-alcoholic fatty liver disease: Design, X-ray co-crystal structure and synthesis of 'first-in-kind' inhibitors of serine/threonine kinase25.,Kiyeleko S, Hocine S, Mautino G, Kuenemann M, Nawrotek A, Miallau L, Vuillard LM, Mirguet O, Kotschy A, Hanessian S Bioorg Med Chem Lett. 2022 Aug 24;75:128950. doi: 10.1016/j.bmcl.2022.128950. PMID:36030002[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Preisinger C, Short B, De Corte V, Bruyneel E, Haas A, Kopajtich R, Gettemans J, Barr FA. YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3zeta. J Cell Biol. 2004 Mar 29;164(7):1009-20. Epub 2004 Mar 22. PMID:15037601 doi:10.1083/jcb.200310061
- ↑ Kiyeleko S, Hocine S, Mautino G, Kuenemann M, Nawrotek A, Miallau L, Vuillard LM, Mirguet O, Kotschy A, Hanessian S. Targeting non-alcoholic fatty liver disease: Design, X-ray co-crystal structure and synthesis of 'first-in-kind' inhibitors of serine/threonine kinase25. Bioorg Med Chem Lett. 2022 Aug 24;75:128950. doi: 10.1016/j.bmcl.2022.128950. PMID:36030002 doi:http://dx.doi.org/10.1016/j.bmcl.2022.128950
