NED-19

NED-19

Identifiers
IUPAC name (1R,3S)-1-[3-[[4-(2-fluorophenyl)piperazin-1-yl]methyl]-4-methoxyphenyl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
CAS Number	1354235-96-3
PubChem CID	1427628
ChemSpider	24604981
ChEBI	CHEBI:138526
ChEMBL	ChEMBL1222013
CompTox Dashboard (EPA)	DTXSID501102307
Chemical and physical data
Formula	C30H31FN4O3
Molar mass	514.601 g·mol−1
3D model (JSmol)	Interactive image
SMILES COC1=C(C=C(C=C1)[C@@H]2C3=C(C[C@H](N2)C(=O)O)C4=CC=CC=C4N3)CN5CCN(CC5)C6=CC=CC=C6F
InChI InChI=1S/C30H31FN4O3/c1-38-27-11-10-19(16-20(27)18-34-12-14-35(15-13-34)26-9-5-3-7-23(26)31)28-29-22(17-25(33-28)30(36)37)21-6-2-4-8-24(21)32-29/h2-11,16,25,28,32-33H,12-15,17-18H2,1H3,(H,36,37)/t25-,28+/m0/s1 Key:FUHCEERDBRGPQZ-LBNVMWSVSA-N

Trans-NED-19 is a drug which acts as a potent and selective antagonist of the endogenous calcium channel opener nicotinic acid adenine dinucleotide phosphate (NAADP), thereby reducing the normal NAADP-mediated calcium flux without blocking calcium channels directly. It is used in research into the functions of NAADP signalling inside many different cell types. ^{[1] [2] [3] [4] [5] [6] [7] [8]}

References

1. Naylor E, Arredouani A, Vasudevan SR, Lewis AM, Parkesh R, Mizote A, et al. (April 2009). "Identification of a chemical probe for NAADP by virtual screening". Nature Chemical Biology. 5 (4): 220–6. doi:10.1038/nchembio.150. PMC   2659327 . PMID   19234453.
2. Rosen D, Lewis AM, Mizote A, Thomas JM, Aley PK, Vasudevan SR, et al. (December 2009). "Analogues of the nicotinic acid adenine dinucleotide phosphate (NAADP) antagonist Ned-19 indicate two binding sites on the NAADP receptor". The Journal of Biological Chemistry. 284 (50): 34930–4. doi: 10.1074/jbc.M109.016519 . PMC   2787355 . PMID   19826006.
3. Park KH, Kim BJ, Shawl AI, Han MK, Lee HC, Kim UH (December 2013). "Autocrine/paracrine function of nicotinic acid adenine dinucleotide phosphate (NAADP) for glucose homeostasis in pancreatic β-cells and adipocytes". The Journal of Biological Chemistry. 288 (49): 35548–58. doi: 10.1074/jbc.M113.489278 . PMC   3853300 . PMID   24165120.
4. Lee S, Paudel O, Jiang Y, Yang XR, Sham JS (March 2015). "CD38 mediates angiotensin II-induced intracellular Ca(2+) release in rat pulmonary arterial smooth muscle cells". American Journal of Respiratory Cell and Molecular Biology. 52 (3): 332–41. doi:10.1165/rcmb.2014-0141OC. PMC   4370261 . PMID   25078456.
5. Davidson SM, Foote K, Kunuthur S, Gosain R, Tan N, Tyser R, et al. (December 2015). "Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore". Cardiovascular Research. 108 (3): 357–66. doi: 10.1093/cvr/cvv226 . PMC   4648198 . PMID   26395965.
6. Pereira GJ, Antonioli M, Hirata H, Ureshino RP, Nascimento AR, Bincoletto C, et al. (February 2017). "Glutamate induces autophagy via the two-pore channels in neural cells". Oncotarget. 8 (8): 12730–12740. doi: 10.18632/oncotarget.14404 . PMC   5355049 . PMID   28055974.
7. Hermann J, Bender M, Schumacher D, Woo MS, Shaposhnykov A, Rosenkranz SC, et al. (2020). "2+ Homeostasis in Mouse Hippocampal Neurons". Frontiers in Cell and Developmental Biology. 8: 496. doi: 10.3389/fcell.2020.00496 . PMC   7333232 . PMID   32676502.
8. Jin X, Zhang Y, Alharbi A, Hanbashi A, Alhoshani A, Parrington J (August 2020). "Targeting Two-Pore Channels: Current Progress and Future Challenges". Trends in Pharmacological Sciences. 41 (8): 582–594. doi: 10.1016/j.tips.2020.06.002 . PMC   7365084 . PMID   32679067.