• Patchliner

    兼顾科研与工业的全自动膜片钳系统
  • Patchliner

    自主生产与质量控制的耗材
  • Patchliner

    拥有超过10年实验设计与支持的经验
  • Dynamite8

    Automated Dynamic Clamp
  • Patchliner

    拥有所有手动膜片钳的特征与优点

2011 - Development of a selective small-molecule inhibitor of Kir1.1, the Renal Outer Medullary Potassium Channel

icon pl  Patchliner publication in Molecular Pharmacology (2011)

Authors: 
Bhave G., Chauder B.A., Liu W., Dawson E.S., Kadakia R., Nguyen T.T., Lewis L.M., Meiler J., Weaver C.D., Satlin L.M., Lindsley C.W., Denton J.S.

 

Journal: 
Molecular Pharmacology (2011) 79(1):42-50


Abstract: 

The renal outer medullary potassium (K+) channel, ROMK (Kir1.1), is a putative drug target for a novel class of loop diuretic that would lower blood volume and pressure without causing hypokalemia. However, the lack of selective ROMK inhibitors has hindered efforts to assess its therapeutic potential. In a high-throughput screen for small-molecule modulators of ROMK, we previously identified a potent and moderately selective ROMK antagonist, 7,13-bis(4-nitrobenzyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (VU590), that also inhibits Kir7.1. Because ROMK and Kir7.1 are coexpressed in the nephron, VU590 is not a good probe of ROMK function in the kidney. Here we describe the development of the structurally related inhibitor 2,2′-oxybis(methylene)bis(5-nitro-1H-benzo[d]imidazole) (VU591), which is as potent as VU590 but is selective for ROMK over Kir7.1 and more than 65 other potential off-targets. VU591 seems to block the intracellular pore of the channel. The development of VU591 may enable studies to explore the viability of ROMK as a diuretic target.


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