Ned 19 is a selective, membrane-permeable, non-competitive NAADP antagonist that inhibits NAADP-mediated Ca2+ signalling with an IC50 value of 65 nM[1] .Ned 19 strongly inhibits tumour growth, angiogenesis and lung metastasis in mice.Ned 19 acts in the concentration range of 25-100 μM for 24-72 hours, decreases the percentage of B16 cells in S phase, increases the percentage in G0/G1 phase, induces apoptosis in a concentration- and time-dependent manner, and reduces cell proliferation.Ned 19 decreases N-adhesin expression and increases E-adhesin expression and affects cell migration behaviour[2].
Ned 19 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Sea urchin egg homogenate
10 µM
3-5 min
Inhibition of NAADP-mediated Ca2+ release
J Biol Chem. 2009 Dec 11;284(50):34930-4
Memory CD4+T cells
50-300 µM
1 hour
Investigated the effect of Ned-19 on TCR-mediated calcium flux, showing stimulation at 50-200 µM and inhibition at 250-300 µM
Molecules. 2024 Feb 19;29(4):907
Sea urchin egg homogenate
65 nM
3-5 min
Inhibition of NAADP-mediated Ca2+ release
J Biol Chem. 2009 Dec 11;284(50):34930-4
Human umbilical vein endothelial cells (HUVECs)
25 µM (cis- and trans-NED 19)
10 minutes
To evaluate the inhibitory effect of NED 19 on histamine-induced [Ca2+]i rise. Results showed that both cis- and trans-NED 19 significantly inhibited histamine-induced [Ca2+]i rise.
To evaluate the inhibitory effect of NED 19 on norepinephrine (NE)-induced [Ca2+]i rise. Results showed that cis- and trans-NED 19 inhibited NE-induced [Ca2+]i rise by approximately 50-60%.
Cells. 2019 Sep 25;8(10):1144
Primary murine CD4+ T cells
various concentrations
16 hours
To assess the role of NAADP signaling in T cell metabolic reprogramming, results showed that trans-Ned 19 inhibited TCR-induced metabolic upregulation.
Cells. 2021 Nov 5;10(11):3039
Human umbilical vein endothelial cells (HUVECs)
100 µM
30 min
Ned-19 abolished VEGF-induced Ca2+ release, impairing phosphorylation of ERK1/2, Akt, eNOS, JNK, cell proliferation, cell migration, and capillary-like tube formation.
Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):E4706-15
Primary murine CD4+ T cells
various concentrations
30 minutes
To assess the role of NAADP signaling in TCR-induced Ca2+ signaling, results showed that trans-Ned 19 inhibited Ca2+ signaling in a concentration-dependent manner.
To evaluate the role of NAADP-dependent acidic Ca2+ stores in VEGF-induced Ca2+ signaling, results showed that Ned-19 concentration-dependently inhibits VEGF-induced Ca2+ release
Sci Rep. 2016 Jan 6;6:18925
Ned 19 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Ischemia-reperfusion injury model
Reperfusion solution
10 μmol/L
60 minutes of reperfusion
To evaluate the effect of Ned-19 on infarct size and left ventricular functional recovery during reperfusion. Results showed that Ned-19 treatment significantly reduced infarct size and improved left ventricular functional recovery in KI mice.
Circulation. 2021 Feb 2;143(5):449-465
Mice
Pancreatic beta cells
Bathing solution
100 μM
30 min pre-incubation
Ned-19 reduced the amplitude of glucose-induced Ca2+ signals in a concentration-dependent manner with an IC50 of 3 μM, demonstrating a key causal link between NAADP signaling and glucose-induced Ca2+ increases.
Nat Chem Biol. 2009 Apr;5(4):220-6
Mice
IL-17A fate mapping mouse model
Intraperitoneal injection
20 mg/kg
Once daily for one week
To assess the effect of NAADP inhibition on the conversion of Th17 cells into regulatory T cells, results showed that trans-Ned 19 promoted the conversion of Th17 cells into regulatory T cells.
Cells. 2021 Nov 5;10(11):3039
C57BL/6 mice
B16 melanoma transplant model
Intraperitoneal injection
5 mg/kg
Every second day for 4 weeks
To evaluate the effect of Ned-19 on tumor growth, vascularization, and metastasis, results showed that Ned-19 significantly inhibited tumor growth, vascularization, and lung metastases
Sci Rep. 2016 Jan 6;6:18925
C57BL/6 mice
Matrigel plug assay
Subcutaneous injection
50, 100, 150 μmol/L
Single injection, duration of 5 days
Ned-19 inhibits VEGF-induced vessel formation in matrigel plugs in mice, with significantly reduced hemoglobin content.
Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):E4706-15
Ned 19 动物研究
Animal study
Administered at a dose of 5 mg/kg/every other day, intraperitoneally for 4 weeks, Ned 19 significantly inhibited tumour growth in a mouse model[2] .
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