SR142948A | CAS#184162-64-9 | neurotensin antagonist

MedKoo Cat#: 563296 | Name: SR142948A

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

SR142948A is a neurotensin antagonist. Antagonizing NTSR2 with SR142948A decreased NTSR2 expression as well as astroglial reactivity.

Chemical Structure

SR142948A

CAS#184162-64-9 (free base)

Theoretical Analysis

MedKoo Cat#: 563296

Name: SR142948A

CAS#: 184162-64-9 (free base)

Chemical Formula: C39H51N5O6

Exact Mass: 685.3839

Molecular Weight: 685.86

Elemental Analysis: C, 68.30; H, 7.50; N, 10.21; O, 14.00

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 700.00	2 weeks

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Related CAS #

184162-64-9 (free base) 184162-21-8 (HCl) 184162-65-0 (sulfate) 184162-66-1 (besylate)

Synonym

SR142948A; SR-142948A; SR 142948A; SR-142948-A; SR 142948 A;

IUPAC/Chemical Name

2-[[5-(2,6-Dimethoxyphenyl)-1-[4-[3-(dimethylamino)propyl-methylcarbamoyl]-2-propan-2-ylphenyl]pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid

InChi Key

LWULHXVBLMWCHO-UHFFFAOYSA-N

InChi Code

InChI=1S/C39H51N5O6/c1-23(2)29-21-26(37(46)43(5)15-9-14-42(3)4)12-13-31(29)44-32(35-33(49-6)10-8-11-34(35)50-7)22-30(41-44)36(45)40-39(38(47)48)27-17-24-16-25(19-27)20-28(39)18-24/h8,10-13,21-25,27-28H,9,14-20H2,1-7H3,(H,40,45)(H,47,48)

SMILES Code

O=C(C1(NC(C2=NN(C3=CC=C(C(N(CCCN(C)C)C)=O)C=C3C(C)C)C(C4=C(OC)C=CC=C4OC)=C2)=O)C5CC6CC(C5)CC1C6)O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO and water

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SR142948A is a potent NT receptor antagonist that binds with high affinity (IC50 = 0.32 - 3.96 nM; Ki < 10 nM).

In vitro activity:

To be determined

In vivo activity:

SR142948A, at a dose that completely blocks the effect of exogenously applied NT on periaqueductal gray neurons, had little effect on their baseline-firing rates, unlike diphenhydramine. SR142948A did block the response to NT and to stimulation of the medial preoptic nucleus. Reference: Neuroscience. 2002;114(4):935-43. https://pubmed.ncbi.nlm.nih.gov/12379249/

	Solvent	mg/mL	mM
Solubility
	DMSO	51.4	75.00
	Water	17.2	25.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 685.86 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Cáceda R, Binder EB, Kinkead B, Nemeroff CB. The role of endogenous neurotensin in psychostimulant-induced disruption of prepulse inhibition and locomotion. Schizophr Res. 2012 Apr;136(1-3):88-95. doi: 10.1016/j.schres.2011.10.013. Epub 2011 Nov 21. PMID: 22104138; PMCID: PMC3595536. 2. Kreitel KD, Swisher CB, Behbehani MM. The effects of diphenhydramine and SR142948A on periaqueductal gray neurons and on the interactions between the medial preoptic nucleus and the periaqueductal gray. Neuroscience. 2002;114(4):935-43. doi: 10.1016/s0306-4522(02)00360-3. PMID: 12379249.

In vitro protocol:

To be determined

In vivo protocol:

1: Kyriatzis G, Bernard A, Bôle A, Pflieger G, Chalas P, Masse M, Lécorché P, Jacquot G, Ferhat L, Khrestchatisky M. Neurotensin receptor 2 is induced in astrocytes and brain endothelial cells in relation to neuroinflammation following pilocarpine-induced seizures in rats. Glia. 2021 Nov;69(11):2618-2643. doi: 10.1002/glia.24062. Epub 2021 Jul 26. PMID: 34310753. 2: Deluigi M, Klipp A, Klenk C, Merklinger L, Eberle SA, Morstein L, Heine P, Mittl PRE, Ernst P, Kamenecka TM, He Y, Vacca S, Egloff P, Honegger A, Plückthun A. Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism. Sci Adv. 2021 Jan 27;7(5):eabe5504. doi: 10.1126/sciadv.abe5504. Erratum in: Sci Adv. 2022 Feb 18;8(7):eabo2407. doi: 10.1126/sciadv.abo2407. PMID: 33571132; PMCID: PMC7840143. 3: Dominguez-Lopez S, Piccart E, Lynch WB, Wollet MB, Sharpe AL, Beckstead MJ. Antagonism of Neurotensin Receptors in the Ventral Tegmental Area Decreases Methamphetamine Self-Administration and Methamphetamine Seeking in Mice. Int J Neuropsychopharmacol. 2018 Apr 1;21(4):361-370. doi: 10.1093/ijnp/pyx117. PMID: 29272412; PMCID: PMC5888879. 4: Kling RC, Plomer M, Lang C, Banerjee A, Hübner H, Gmeiner P. Development of Covalent Ligand-Receptor Pairs to Study the Binding Properties of Nonpeptidic Neurotensin Receptor 1 Antagonists. ACS Chem Biol. 2016 Apr 15;11(4):869-75. doi: 10.1021/acschembio.5b00965. Epub 2016 Jan 27. PMID: 26808719. 5: Bose P, Rompré PP, Warren RA. Neurotensin enhances glutamatergic EPSCs in VTA neurons by acting on different neurotensin receptors. Peptides. 2015 Nov;73:43-50. doi: 10.1016/j.peptides.2015.08.008. Epub 2015 Aug 18. PMID: 26296323. 6: Dijkman PM, Watts A. Lipid modulation of early G protein-coupled receptor signalling events. Biochim Biophys Acta. 2015 Nov;1848(11 Pt A):2889-97. doi: 10.1016/j.bbamem.2015.08.004. Epub 2015 Aug 11. PMID: 26275588. 7: Thomas JB, Giddings AM, Olepu S, Wiethe RW, Harris DL, Narayanan S, Warner KR, Sarret P, Longpre JM, Runyon SP, Gilmour BP. Identification of N-{[6-chloro-4-(2,6-dimethoxyphenyl)quinazolin-2-yl]carbonyl}-l-leucine (NTRC-808), a novel nonpeptide chemotype selective for the neurotensin receptor type 2. Bioorg Med Chem Lett. 2015 Jan 15;25(2):292-6. doi: 10.1016/j.bmcl.2014.11.047. Epub 2014 Nov 24. PMID: 25499438; PMCID: PMC4296974. 8: Peddibhotla S, Hedrick MP, Hershberger P, Maloney PR, Li Y, Milewski M, Gosalia P, Gray W, Mehta A, Sugarman E, Hood B, Suyama E, Nguyen K, Heynen-Genel S, Vasile S, Salaniwal S, Stonich D, Su Y, Mangravita-Novo A, Vicchiarelli M, Roth GP, Smith LH, Chung TD, Hanson GR, Thomas JB, Caron MG, Barak LS, Pinkerton AB. Discovery of ML314, a Brain Penetrant Non-Peptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor. ACS Med Chem Lett. 2013 Jul 20;4(9):846-851. doi: 10.1021/ml400176n. PMID: 24611085; PMCID: PMC3940307. 9: Lang C, Maschauer S, Hübner H, Gmeiner P, Prante O. Synthesis and evaluation of a (18)F-labeled diarylpyrazole glycoconjugate for the imaging of NTS1-positive tumors. J Med Chem. 2013 Nov 27;56(22):9361-5. doi: 10.1021/jm401491e. Epub 2013 Nov 6. PMID: 24160350. 10: Cáceda R, Binder EB, Kinkead B, Nemeroff CB. The role of endogenous neurotensin in psychostimulant-induced disruption of prepulse inhibition and locomotion. Schizophr Res. 2012 Apr;136(1-3):88-95. doi: 10.1016/j.schres.2011.10.013. Epub 2011 Nov 21. PMID: 22104138; PMCID: PMC3595536. 11: Kadiri N, Rodeau JL, Schlichter R, Hugel S. Neurotensin inhibits background K+ channels and facilitates glutamatergic transmission in rat spinal cord dorsal horn. Eur J Neurosci. 2011 Oct;34(8):1230-40. doi: 10.1111/j.1460-9568.2011.07846.x. Epub 2011 Sep 21. PMID: 21936876. 12: Lafrance M, Roussy G, Belleville K, Maeno H, Beaudet N, Wada K, Sarret P. Involvement of NTS2 receptors in stress-induced analgesia. Neuroscience. 2010 Mar 17;166(2):639-52. doi: 10.1016/j.neuroscience.2009.12.042. Epub 2009 Dec 24. PMID: 20035838. 13: Mitchell VA, Kawahara H, Vaughan CW. Neurotensin inhibition of GABAergic transmission via mGluR-induced endocannabinoid signalling in rat periaqueductal grey. J Physiol. 2009 Jun 1;587(Pt 11):2511-20. doi: 10.1113/jphysiol.2008.167429. Epub 2009 Apr 9. PMID: 19359367; PMCID: PMC2714017. 14: Norman C, Grimond-Billa SK, Bennett GW, Cassaday HJ. A neurotensin agonist and antagonist decrease and increase activity, respectively, but do not preclude discrete cue conditioning. J Psychopharmacol. 2010 Mar;24(3):373-81. doi: 10.1177/0269881108097721. Epub 2008 Oct 6. PMID: 18838494. 15: Marie-Claire C, Palminteri S, Romualdi P, Noble F. Effects of the selective neurotensin antagonist SR 142948A on 3,4-methylenedioxymethamphetamine-induced behaviours in mice. Neuropharmacology. 2008 Jun;54(7):1107-11. doi: 10.1016/j.neuropharm.2008.03.001. Epub 2008 Mar 8. PMID: 18410947. 16: Xue Y, Chen L, Cui QL, Xie JX, Yung WH. Electrophysiological and behavioral effects of neurotensin in rat globus pallidus: an in vivo study. Exp Neurol. 2007 May;205(1):108-15. doi: 10.1016/j.expneurol.2007.01.031. Epub 2007 Feb 13. PMID: 17362935. 17: Azmi N, Norman C, Spicer CH, Bennett GW. Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task. Behav Pharmacol. 2006 Jun;17(4):357-62. doi: 10.1097/01.fbp.0000224382.63744.20. PMID: 16914954. 18: Kreitel KD, Swisher CB, Behbehani MM. The effects of diphenhydramine and SR142948A on periaqueductal gray neurons and on the interactions between the medial preoptic nucleus and the periaqueductal gray. Neuroscience. 2002;114(4):935-43. doi: 10.1016/s0306-4522(02)00360-3. PMID: 12379249. 19: Meyer-Spasche A, Reed HE, Piggins HD. Neurotensin phase-shifts the firing rate rhythm of neurons in the rat suprachiasmatic nuclei in vitro. Eur J Neurosci. 2002 Jul;16(2):339-44. doi: 10.1046/j.1460-9568.2002.02067.x. PMID: 12169114. 20: Binder EB, Gross RE, Nemeroff CB, Kilts CD. Effects of neurotensin receptor antagonism on latent inhibition in Sprague-Dawley rats. Psychopharmacology (Berl). 2002 May;161(3):288-95. doi: 10.1007/s00213-002-1031-4. Epub 2002 Apr 4. PMID: 12021832.