Why are most phospholipidosis inducers also hERG blockers?
作者: Svetoslav SlavovIva Stoyanova-SlavovaShuaizhang LiJinghua ZhaoRuili HuangMenghang XiaRichard Beger
作者单位: 1National Center for Toxicological Research
2National Center for Advancing Translational Sciences
刊名: Archives of Toxicology, 2017, Vol.91 (12), pp.3885-3895
来源数据库: Springer Journal
DOI: 10.1007/s00204-017-1995-9
关键词: Human Ether-à-go-go related genePhospholipidosis3D-SDARToxicophoreMolecular modeling
英文摘要: Recent reports have noted that a number of compounds that block the human Ether-à-go-go related gene (hERG) ion channel also induce phospholipidosis (PLD). To explore a hypothesis explaining why most PLD inducers are also hERG inhibitors, a modeling approach was undertaken with data sets comprised of 4096 compounds assayed for hERG inhibition and 5490 compounds assayed for PLD induction. To eliminate the chemical domain effect, a filtered data set of 567 compounds tested in quantitative high-throughput screening (qHTS) format for both hERG inhibition and PLD induction was constructed. Partial least squares (PLS) modeling followed by 3D-SDAR mapping of the most frequently occurring bins and projection on to the chemical structure suggested that both adverse effects are driven by similar...
原始语种摘要: Recent reports have noted that a number of compounds that block the human Ether-à-go-go related gene (hERG) ion channel also induce phospholipidosis (PLD). To explore a hypothesis explaining why most PLD inducers are also hERG inhibitors, a modeling approach was undertaken with data sets comprised of 4096 compounds assayed for hERG inhibition and 5490 compounds assayed for PLD induction. To eliminate the chemical domain effect, a filtered data set of 567 compounds tested in quantitative high-throughput screening (qHTS) format for both hERG inhibition and PLD induction was constructed. Partial least squares (PLS) modeling followed by 3D-SDAR mapping of the most frequently occurring bins and projection on to the chemical structure suggested that both adverse effects are driven by similar...
全文获取路径: Springer  (合作)
分享到:
来源刊物:
影响因子:5.215 (2012)

×
关键词翻译
关键词翻译
  • chemical 化学的
  • compounds 化合物
  • effects 海员自身物品
  • activity 活度
  • removal 消去
  • suggested 建议
  • achieved 获得的
  • modeling 制祝型
  • values 价值观
  • hypothesis 假说