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Small-molecule WNK inhibition regulates cardiovascular and renal function.
Yamada, Ken; Park, Hyi-Man; Rigel, Dean F; DiPetrillo, Keith; Whalen, Erin J; Anisowicz, Anthony; Beil, Michael; Berstler, James; Brocklehurst, Cara Emily; Burdick, Debra A; Caplan, Shari L; Capparelli, Michael P; Chen, Guanjing; Chen, Wei; Dale, Bethany; Deng, Lin; Fu, Fumin; Hamamatsu, Norio; Harasaki, Kouki; Herr, Tracey; Hoffmann, Peter; Hu, Qi-Ying; Huang, Waan-Jeng; Idamakanti, Neeraja; Imase, Hidetomo; Iwaki, Yuki; Jain, Monish; Jeyaseelan, Jey; Kato, Mitsunori; Kaushik, Virendar K; Kohls, Darcy; Kunjathoor, Vidya; LaSala, Daniel; Lee, Jongchan; Liu, Jing; Luo, Yang; Ma, Fupeng; Mo, Ruowei; Mowbray, Sarah; Mogi, Muneto; Ossola, Flavio; Pandey, Pramod; Patel, Sejal J; Raghavan, Swetha; Salem, Bahaa; Shanado, Yuka H; Trakshel, Gary M; Turner, Gordon; Wakai, Hiromichi; Wang, Chunhua.
Afiliação
  • Yamada K; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Park HM; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Rigel DF; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • DiPetrillo K; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Whalen EJ; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Anisowicz A; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Beil M; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Berstler J; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Brocklehurst CE; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Burdick DA; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Caplan SL; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Capparelli MP; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Chen G; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Chen W; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Dale B; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Deng L; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Fu F; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Hamamatsu N; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Harasaki K; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Herr T; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Hoffmann P; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Hu QY; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Huang WJ; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Idamakanti N; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Imase H; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Iwaki Y; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Jain M; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Jeyaseelan J; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Kato M; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Kaushik VK; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Kohls D; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Kunjathoor V; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • LaSala D; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Lee J; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Liu J; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Luo Y; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Ma F; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Mo R; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Mowbray S; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Mogi M; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Ossola F; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Pandey P; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Patel SJ; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Raghavan S; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Salem B; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Shanado YH; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Trakshel GM; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Turner G; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Wakai H; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
  • Wang C; Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
Nat Chem Biol ; 12(11): 896-898, 2016 Nov.
Article em En | MEDLINE | ID: mdl-27595330
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirrolidinas / Sistema Cardiovascular / Proteínas Serina-Treonina Quinases / Inibidores de Proteínas Quinases / Bibliotecas de Moléculas Pequenas / Imidazóis / Rim Limite: Animals / Humans Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pirrolidinas / Sistema Cardiovascular / Proteínas Serina-Treonina Quinases / Inibidores de Proteínas Quinases / Bibliotecas de Moléculas Pequenas / Imidazóis / Rim Limite: Animals / Humans Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos