Einsiedel J, Held C, Hervet M, Plomer M, Tschammer N, Hübner H, Gmeiner P (2011)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2011
Original Authors: Einsiedel J., Held C., Hervet M., Plomer M., Tschammer N., Hubner H., Gmeiner P.
Publisher: American Chemical Society
Book Volume: 54
Pages Range: 2915-2923
Journal Issue: 8
DOI: 10.1021/jm200006c
The neurotensin receptor subtype 2 (NTS2) is involved in the modulation of tonic pain sensitivity and psychiatric diseases and is, therefore, regarded as a highly attractive pharmacological target protein. Aiming to discover NTS2 selective ligands, we herein describe the identification of screening hits and the chemical synthesis of structural variants leading to the highly potent and NTS2 selective peptide-peptoid hybrids of type 3. The neurotensin mimetics 3a and 3e-g incorporating an N-(4-hydroxyphenethyl)glycine substructure exhibit single digit nanomolar affinity (K = 4.3-8.8 nM) and 1900-12000 fold selectivity over the neurotensin receptor subtype 1 (NTS1). According to functional experiments, the test compounds 3a and 3e-g displayed an inhibition of constitutive mitogen-activated protein kinase (MAPK) activity exceeding 2.6-4.6 times the inverse agonist activity of the endogenous ligand neurotensin. © 2011 American Chemical Society.
APA:
Einsiedel, J., Held, C., Hervet, M., Plomer, M., Tschammer, N., Hübner, H., & Gmeiner, P. (2011). Discovery of highly potent and neurotensin receptor 2 selective neurotensin mimetics. Journal of Medicinal Chemistry, 54(8), 2915-2923. https://doi.org/10.1021/jm200006c
MLA:
Einsiedel, Jürgen, et al. "Discovery of highly potent and neurotensin receptor 2 selective neurotensin mimetics." Journal of Medicinal Chemistry 54.8 (2011): 2915-2923.
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