5DRB

Small-molecule WNK inhibition regulates cardiovascular and renal function.

Yamada, K., Park, H.M., Rigel, D.F., DiPetrillo, K., Whalen, E.J., Anisowicz, A., Beil, M., Berstler, J., Brocklehurst, C.E., Burdick, D.A., Caplan, S.L., Capparelli, M.P., Chen, G., Chen, W., Dale, B., Deng, L., Fu, F., Hamamatsu, N., Harasaki, K., Herr, T., Hoffmann, P., Hu, Q.Y., Huang, W.J., Idamakanti, N., Imase, H., Iwaki, Y., Jain, M., Jeyaseelan, J., Kato, M., Kaushik, V.K., Kohls, D., Kunjathoor, V., LaSala, D., Lee, J., Liu, J., Luo, Y., Ma, F., Mo, R., Mowbray, S., Mogi, M., Ossola, F., Pandey, P., Patel, S.J., Raghavan, S., Salem, B., Shanado, Y.H., Trakshel, G.M., Turner, G., Wakai, H., Wang, C., Weldon, S., Wielicki, J.B., Xie, X., Xu, L., Yagi, Y.I., Yasoshima, K., Yin, J., Yowe, D., Zhang, J.H., Zheng, G., Monovich, L.

(2016) Nat Chem Biol 12: 896-898

• PubMed: 27595330 Search on PubMed
• DOI: https://doi.org/10.1038/nchembio.2168
• Primary Citation of Related Structures:  
  5DRB


• PubMed Abstract: 
  

  The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electro-lyte homeostasis, consistent with WNK-kinase-associated physiology and pathophysiology.

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Organizational Affiliation: 

Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.