Targeting renal epithelial channels for the control of insect vectors

作者: Klaus W Beyenbach , Yasong Yu , Peter M Piermarini , Jerod Denton

DOI: 10.1080/21688370.2015.1081861

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摘要: Three small molecules were identified in high throughput screens that 1) block renal inward rectifier potassium (Kir) channels of Aedes aegypti expressed HEK cells and Xenopus oocytes, 2) inhibit the secretion KCl but not NaCl isolated Malpighian tubules, after injection into hemolymph, 3) excretion vivo, 4) render mosquitoes flightless or dead within 24h. Some had swollen abdomens at death consistent with failure. VU625, most potent promising molecule for development as mosquitocide, inhibits AeKir1-mediated currents an IC50 less than 100 nM. It is highly selective AeKir1 over mammalian Kir channels, it affects only 3 68 membrane proteins. These results document failure a new mode-of-action mosquitocide development, molecular target inducing failure, promise discovery species-specific insecticides.

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