trans-Ned 19

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a dinucleotide second messenger that triggers the release of calcium from lysosomes and related cellular compartments. trans-Ned-19 is a structural analog of NAADP that blocks NAADP-dependent calcium release (IC50 = 6 nM) as well as NAADP binding to sea urchin egg homogenate (IC50 = 0.4 nM). The trans form of Ned-19 is significantly more potent than the cis isomer in both assays. Ned-19 does not affect either IP3-mediated calcium release or cyclic ADP-ribose-mediated calcium release. It directly binds NAADP receptors on lysosomes in mouse pancreatic beta cells and competitively antagonizes activation by NAADP. It inhibits glucose-induced calcium oscillations in pancreatic islets and insulin-induced calcium increases in 3T3-L1 adipocytes. Ned-19 also blocks calcium signaling induced by endothelin-1 or norepinephrine in renal afferent arterioles. Ned-19 dose-dependently reduces infection of host cells by Ebola virus.