Target Validation Information
TTD ID	T02728
Target Name	Neurotensin receptor type 1 (NTSR1)
Type of Target	Clinical trial
Drug Potency against Target	CGX-1160	Drug Info	IC50 = 500 nM	[7]
	4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	Drug Info	Ki < 1000 nM	[5]
	Demotensin 1	Drug Info	IC50 = 0.32 nM	[1]
	Demotensin 2	Drug Info	IC50 = 0.41 nM	[1]
	Demotensin 3	Drug Info	IC50 = 1.5 nM	[1]
	Demotensin 4	Drug Info	IC50 = 0.85 nM	[1]
	H-Arg-Arg-Pro-Tyr-Ile-Aac-OH	Drug Info	Ki = 2.4 nM	[3]
	H-Arg-Arg-Pro-Tyr-Ile-N-Me-Leu-OH	Drug Info	Ki = 190 nM	[3]
	H-Arg-Arg-Pro-Tyr-N-Me-Ile-Leu-OH	Drug Info	Ki = 160 nM	[3]
	H-Arg-N-Me-Arg-Pro-Tyr-Ile-Leu-OH	Drug Info	Ki = 0.51 nM	[3]
	Meclinertant	Drug Info	IC50 = 0.99 nM	[4]
	NEUROTENSIN	Drug Info	IC50 = 1.4 nM	[2]
	Neurotensin(8-13)	Drug Info	Ki = 0.14 nM	[4]
Action against Disease Model	Meclinertant	Drug Info	SR48692 (a non-peptide NT receptor antagonist) bound with high affinity (IC(50) = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific (125)I-NT binding with high affinity (IC(50) values of 2 and 200 nM). SR48692 (5 microM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 microM SR48692, reduced NCI-H209 colony n uMber. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT(1) receptor antagonist which inhibits SCLC growth.	[6]
References
REF 1	Toward stable N4-modified neurotensins for NTS1-receptor-targeted tumor imaging with 99mTc. J Med Chem. 2006 Jul 27;49(15):4767-76.
REF 2	Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
REF 3	Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1, ligand backbone methylations and molecular modeling of neurotensi... Bioorg Med Chem. 2008 Oct 15;16(20):9359-68.
REF 4	Comparison of N-terminal modifications on neurotensin(8-13) analogues correlates peptide stability but not binding affinity with in vivo efficacy. J Med Chem. 2009 Apr 9;52(7):1803-13.
REF 5	Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
REF 6	SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells. Peptides. 2001 Jan;22(1):109-15.
REF 7	Therapeutic potential of venom peptides. Nat Rev Drug Discov. 2003 Oct;2(10):790-802.

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