Acetylneurotensin-(8-31) is the shortest analog of neurotensin with full binding and pharmacological activities[1].
ML314 is a potent molecule agonist of NTR1 (EC50 = 1.9 μM); showed good selectivity against NTR2 and GPR35, but did not stimulate Ca2+ mobilization.IC50 value: 1.9 uM (EC50) [1]Target: NTR1 agonistMedicinal chemistry optimization of MLS-0233108 led to ML314, the most potent molecule in this second series that exhibited full agonist behavior (100 %) on NTR1 (EC50 = 1.9 μM). ML314 showed good selectivity against NTR2 and GPR35, but did not stimulate Ca2+ mobilization. ML314 is potentially a biased agonist operating via the β-arrestin pathway rather than the traditional Gq coupled pathway. Signaling mediated by β-arrestin has distinct biochemical and functional consequences that may lead to physiological advantages as described below. This probe report describes the discovery and properties of ML301 and summarizes the HTS and follow-up campaign, which identified ML314.
(S)-Osanetant is the S-enantiomer of Osanetant. Osanetant (SR142801) is a selective NK3 receptor antagonist. Osanetant produces anxiolytic- and antidepressant-like effects and is researched for schizophrenia[1].
THX-B is a potent and non-peptidic p75NTR (neurotrophin receptor p75) antagonist. THX-B can be used in the research of diabetic kidney disease, neurodegenerative and inflammatory disorders[1][2][3].
Neurotensin, a gut tridecapeptide, acts as a potent cellular mitogen for various colorectal and pancreatic cancers which possess high-affinity neurotensin receptors (NTR).
Levocabastine (R 50547) is a potent and selective histamine H1-receptor antagonist. Levocabastine hydrochloride is also a selective, high affinity neurotensin receptor subtype 2 (NTR2) antagonist, with a Ki of 17 nM for mNTR2. Levocabastine can act as a VLA-4 antagonist, interferes with conjunctival eosinophil infiltration in allergic conjunctivitis (AC)[1][2][3].
Levocabastine (R 50547) hydrochloride is a long acting, highly potent and selective histamine H1-receptor antagonist with anti-allergic activity. Levocabastine hydrochloride is also a selective, high affinity neurotensin receptor subtype 2 (NTR2) antagonist, with a Ki of 17 nM for mNTR2[1][2].
[D-Trp11]-Neurotensin, an analogue of Neurotensin (NT), is a selective antagonist of NT in perfused rat hearts but behaves as a full agonist in guinea pig atria and rat stomach strips. [D-Trp11]-Neurotensin can inhibit NT-induced hypotension[1][2].
SORT-PGRN interaction inhibitor 1 is a potent inhibitor of the sortilin-progranulin interaction with an IC50 of 2 μM[1].
BVFP binds to the PGRN588–593 peptide with a Kd of 20 μM. BVFP can disrupt PGRN-SORT1 binding. BVFP also inhibits SORT1-mediated rPGRN endocytosis[1].
NTRC-824 (Compound 5) is a potent, selective and neurotensin-like nonpeptide neurotensin receptor type 2 (NTS2) antagonist with an IC50 of 38 nM and a Ki of 202 nM. NTRC-824 is >150-fold selectivity for NTS2 over NTS1 (Ki >30 μM)[1].
SR 142948 is an orally active, potent and selective non-peptide neurotensin receptor (NT1R) antagonist. SR 142948 antagonizes NT-induced inositol monophosphate formation in HT 29 cells with an IC50 of 3.9 nM. SR 142948 blocks hypothermia, analgesia and steering behavior induced by NT in vivo. SR 142948 shows blood-brain permeability, can be used in study of psychiatric disorders[1][2].
Sortilin antagonist 1 (compound 44) is a sortilin antagonist with an IC50 value of 20 nM for inhibiting Neurotensin (NTS) binds to sortilin. Neurotensin is a sortilin ligand. Sortilin antagonist 1 can be used for the research of neurological disease[1].
Kinetensin is a neurotensin-like peptide isolated from pepsin-treated human plasma.
Meclinertant (SR 48692) is a potent, selective, nonpeptide and orally active neurotensin receptor 1 (NTS1) antagonist. In human colon carcinoma (HT-29) cells, Meclinertant competitively antagonizes neurotensin-induced intracellular Ca2+ mobilization with a pA2 values of 8.13. Meclinertant has anxiolytic, anti-addictive and memory-impairing effects[1][2][3].
Zendusortide is a sortilin binding peptide[1].
[Lys8, Lys9]-Neurotensin (8-13) (JMV438), a Neurotensin analog, exerts its analgesic effects through activation of the G protein-coupled receptors NTS1 and NTS2, with Ki values of 0.33 nM and 0.95 nM for hNTS1 and hNTS2 receptors, respectively[1].
SBI-553 is a potent and brain penetrant NTR1 allosteric modulator, with an EC50 of 0.34 μM[1].
SORT-PGRN interaction inhibitor 3 (Compound 13) is a SORT-PGRN interaction inhibitor (IC50: 0.17 μM). SORT-PGRN interaction inhibitor 3 can be used for research of neurodegenerative diseases[1].
Contulakin G is an O-glycosylated invertebrate neurotensin. Contulakin-G is a weaker agonist for the neurotensin receptor. Contulakin G is also a potent antinociceptive agent[1][2].
JMV 449 is a potent neurotensin receptor agonist. JMV 449 shows an IC50 of 0.5 nM in binding to mouse brain membranes and an EC50 of 1.9 nM in contracting the guinea-pig ileum. JMV 449 has highly potent and long-lasting hypothermic and analgesic effects in the mouse[1][2].