SHA-68 | CAS# 847553-89-3 | NPSR antagonist

MedKoo Cat#: 574404 | Name: SHA-68

Description:

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

SHA-68 is a selective neuropeptide S receptor (NPSR) antagonist that displays no activity against a range of 14 GPCRs, including vasopressin and oxytocin receptors.

Chemical Structure

SHA-68

CAS#847553-89-3

Theoretical Analysis

MedKoo Cat#: 574404

Name: SHA-68

CAS#: 847553-89-3

Chemical Formula: C26H24FN3O3

Exact Mass: 445.1802

Molecular Weight: 445.49

Elemental Analysis: C, 70.10; H, 5.43; F, 4.26; N, 9.43; O, 10.77

Price and Availability

Size	Price	Availability
25mg	USD 550.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
1g	USD 4,650.00	2 Weeks

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Related CAS #

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Synonym

SHA-68; SHA68; SHA 68

IUPAC/Chemical Name

N-[(4-Fluorophenyl)methyl]tetrahydro-3-oxo-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxamide

InChi Key

SFRQIPRTNYHJHP-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H24FN3O3/c27-22-13-11-19(12-14-22)17-28-24(31)29-15-16-30-23(18-29)26(33-25(30)32,20-7-3-1-4-8-20)21-9-5-2-6-10-21/h1-14,23H,15-18H2,(H,28,31)

SMILES Code

O=C(N1CC2N(C(OC2(C3=CC=CC=C3)C4=CC=CC=C4)=O)CC1)NCC5=CC=C(F)C=C5

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, DMF, and ethanol

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:

SHA-68 is an antagonist of the neuropeptide S receptor (NPSR; IC50s = 22 and 23.8 nM for the NPSR Asn107 and NPSR Ile107 isoforms, respectively). It is selective for NPSR over a panel of 14 G protein-coupled receptors exhibiting no activity at a concentration of 10 μM.

In vitro activity:

NPSR antagonists, one being SHA-68, block NPS-induced chemoattraction, with SHA-68 being more potent. This effect is specific to NPSR activation, as the antagonists do not alter random cell migration Reference: Peptides. 2013 Jan;39:16-20. https://pubmed.ncbi.nlm.nih.gov/23142110/

In vivo activity:

SHA-68 is suitable for studying in vivo NPS actions, but its utility is hampered by poor pharmacokinetics. In mouse locomotor experiments, SHA-68 countered NPS-induced stimulant effects, but not those of caffeine. It fully prevented NPS arousal in the mouse righting reflex assay. Anxiolytic-like effects of NPS were slightly reduced in the mouse open field by SHA-68. SHA-68 had limited activity in countering NPS's inhibitory effect on food intake in rats and lacked intrinsic effects in all assays. Reference: Peptides. 2010 May;31(5):915-25. https://pubmed.ncbi.nlm.nih.gov/20172007/

	Solvent	mg/mL	mM
Solubility
	DMF	16.0	35.92
	DMSO	14.0	31.43
	Ethanol	20.0	44.89

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 445.49 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. Filaferro M, Novi C, Ruggieri V, Genedani S, Alboni S, Malagoli D, Caló G, Guerrini R, Vitale G. Neuropeptide S stimulates human monocyte chemotaxis via NPS receptor activation. Peptides. 2013 Jan;39:16-20. doi: 10.1016/j.peptides.2012.10.013. Epub 2012 Nov 8. PMID: 23142110. 2. Ruzza C, Rizzi A, Trapella C, Pela' M, Camarda V, Ruggieri V, Filaferro M, Cifani C, Reinscheid RK, Vitale G, Ciccocioppo R, Salvadori S, Guerrini R, Calo' G. Further studies on the pharmacological profile of the neuropeptide S receptor antagonist SHA 68. Peptides. 2010 May;31(5):915-25. doi: 10.1016/j.peptides.2010.02.012. Epub 2010 Feb 19. PMID: 20172007. 3. Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK. Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor. J Pharmacol Exp Ther. 2008 Jun;325(3):893-901. doi: 10.1124/jpet.107.135103. Epub 2008 Mar 12. PMID: 18337476; PMCID: PMC2583099.

In vitro protocol:

In vivo protocol:

1. Ruzza C, Rizzi A, Trapella C, Pela' M, Camarda V, Ruggieri V, Filaferro M, Cifani C, Reinscheid RK, Vitale G, Ciccocioppo R, Salvadori S, Guerrini R, Calo' G. Further studies on the pharmacological profile of the neuropeptide S receptor antagonist SHA 68. Peptides. 2010 May;31(5):915-25. doi: 10.1016/j.peptides.2010.02.012. Epub 2010 Feb 19. PMID: 20172007. 2. Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK. Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor. J Pharmacol Exp Ther. 2008 Jun;325(3):893-901. doi: 10.1124/jpet.107.135103. Epub 2008 Mar 12. PMID: 18337476; PMCID: PMC2583099.

1: Okamura N, Habay SA, Zeng J, Chamberlin AR, Reinscheid RK. Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro- oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor. J Pharmacol Exp Ther. 2008 Jun;325(3):893-901. doi: 10.1124/jpet.107.135103. Epub 2008 Mar 12. PMID: 18337476; PMCID: PMC2583099. 2: Guerrini R, Salvadori S, Rizzi A, Regoli D, Calo' G. Neurobiology, pharmacology, and medicinal chemistry of neuropeptide S and its receptor. Med Res Rev. 2010 Sep;30(5):751-77. doi: 10.1002/med.20180. PMID: 19824051. 3: Ruzza C, Rizzi A, Trapella C, Pela' M, Camarda V, Ruggieri V, Filaferro M, Cifani C, Reinscheid RK, Vitale G, Ciccocioppo R, Salvadori S, Guerrini R, Calo' G. Further studies on the pharmacological profile of the neuropeptide S receptor antagonist SHA 68. Peptides. 2010 May;31(5):915-25. doi: 10.1016/j.peptides.2010.02.012. Epub 2010 Feb 19. PMID: 20172007. 4: Kallupi M, Cannella N, Economidou D, Ubaldi M, Ruggeri B, Weiss F, Massi M, Marugan J, Heilig M, Bonnavion P, de Lecea L, Ciccocioppo R. Neuropeptide S facilitates cue-induced relapse to cocaine seeking through activation of the hypothalamic hypocretin system. Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19567-72. doi: 10.1073/pnas.1004100107. Epub 2010 Oct 25. PMID: 20974945; PMCID: PMC2984152. 5: Trapella C, Pela M, Del Zoppo L, Calo G, Camarda V, Ruzza C, Cavazzini A, Costa V, Bertolasi V, Reinscheid RK, Salvadori S, Guerrini R. Synthesis and separation of the enantiomers of the neuropeptide S receptor antagonist (9R/S)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68). J Med Chem. 2011 Apr 28;54(8):2738-44. doi: 10.1021/jm200138r. Epub 2011 Apr 5. PMID: 21466221; PMCID: PMC3095364. 6: Filaferro M, Novi C, Ruggieri V, Genedani S, Alboni S, Malagoli D, Caló G, Guerrini R, Vitale G. Neuropeptide S stimulates human monocyte chemotaxis via NPS receptor activation. Peptides. 2013 Jan;39:16-20. doi: 10.1016/j.peptides.2012.10.013. Epub 2012 Nov 8. PMID: 23142110. 7: Gardella E, Romei C, Cavallero A, Trapella C, Fedele E, Raiteri L. Neuropeptide S inhibits release of 5-HT and glycine in mouse amygdala and frontal/prefrontal cortex through activation of the neuropeptide S receptor. Neurochem Int. 2013 Mar;62(4):360-6. doi: 10.1016/j.neuint.2013.02.003. Epub 2013 Feb 11. PMID: 23411412. 8: Han RW, Zhang RS, Xu HJ, Chang M, Peng YL, Wang R. Neuropeptide S enhances memory and mitigates memory impairment induced by MK801, scopolamine or Aβ₁₋₄₂ in mice novel object and object location recognition tasks. Neuropharmacology. 2013 Jul;70:261-7. doi: 10.1016/j.neuropharm.2013.02.002. Epub 2013 Feb 21. PMID: 23454528. 9: Hassler C, Zhang Y, Gilmour B, Graf T, Fennell T, Snyder R, Deschamps JR, Reinscheid RK, Garau C, Runyon SP. Identification of neuropeptide S antagonists: structure-activity relationship studies, X-ray crystallography, and in vivo evaluation. ACS Chem Neurosci. 2014 Aug 20;5(8):731-44. doi: 10.1021/cn500113c. Epub 2014 Jul 11. PMID: 24964000; PMCID: PMC4140596. 10: Ruzza C, Rizzi A, Malfacini D, Pulga A, Pacifico S, Salvadori S, Trapella C, Reinscheid RK, Calo G, Guerrini R. In vitro and in vivo pharmacological characterization of a neuropeptide S tetrabranched derivative. Pharmacol Res Perspect. 2015 Feb;3(1):e00108. doi: 10.1002/prp2.108. Epub 2015 Jan 5. PMID: 25692025; PMCID: PMC4317238. 11: Ruzza C, Asth L, Guerrini R, Trapella C, Gavioli EC. Neuropeptide S reduces mouse aggressiveness in the resident/intruder test through selective activation of the neuropeptide S receptor. Neuropharmacology. 2015 Oct;97:1-6. doi: 10.1016/j.neuropharm.2015.05.002. Epub 2015 May 13. PMID: 25979487. 12: Li MS, Peng YL, Jiang JH, Xue HX, Wang P, Zhang PJ, Han RW, Chang M, Wang R. Neuropeptide S Increases locomotion activity through corticotropin-releasing factor receptor 1 in substantia nigra of mice. Peptides. 2015 Sep;71:196-201. doi: 10.1016/j.peptides.2015.07.024. Epub 2015 Jul 31. PMID: 26239581. 13: Yang F, Peng L, Luo J, Yi H, Hu X. Intra-amygdala microinfusion of neuropeptide S attenuates neuropathic pain and suppresses the response of spinal microglia and astrocytes after spinal nerve ligation in rats. Peptides. 2016 Aug;82:26-34. doi: 10.1016/j.peptides.2016.05.005. Epub 2016 May 17. PMID: 27224019. 14: Roncacè V, Polli FS, Zojicic M, Kohlmeier KA. Neuropeptide S (NPS) is a neuropeptide with cellular actions in arousal and anxiety-related nuclei: Functional implications for effects of NPS on wakefulness and mood. Neuropharmacology. 2017 Nov;126:292-317. doi: 10.1016/j.neuropharm.2017.06.025. Epub 2017 Jun 24. PMID: 28655610. 15: Wang C, Xin L, Cai CC, Cong CY, Xie JF, Kong XP, Dong CY, Li J, Cui GF, Chen HL, Ren YL, Shao YF, Hou YP. Neuropeptide S Displays as a Key Neuromodulator in Olfactory Spatial Memory. Chem Senses. 2020 Apr 17;45(3):195-202. doi: 10.1093/chemse/bjaa003. PMID: 32010937. 16: Albanese V, Ruzza C, Marzola E, Bernardi T, Fabbri M, Fantinati A, Trapella C, Reinscheid RK, Ferrari F, Sturaro C, Calò G, Amendola G, Cosconati S, Pacifico S, Guerrini R, Preti D. Structure-Activity Relationship Studies on Oxazolo[3,4-a]pyrazine Derivatives Leading to the Discovery of a Novel Neuropeptide S Receptor Antagonist with Potent In Vivo Activity. J Med Chem. 2021 Apr 8;64(7):4089-4108. doi: 10.1021/acs.jmedchem.0c02223. Epub 2021 Mar 18. PMID: 33733768; PMCID: PMC8041306. 17: Zarkin A, Jahan R, Uprety R, Zhang Y, McElhinny C, Snyder R, Gay E, Jewula G, Bool H, Clark SD, Runyon S. Identification of a Novel Neuropeptide S Receptor Antagonist Scaffold Based on the SHA-68 Core. Pharmaceuticals (Basel). 2021 Oct 6;14(10):1024. doi: 10.3390/ph14101024. PMID: 34681248; PMCID: PMC8538004. 18: Piwowarczyk-Nowak A, Pałasz A, Suszka-Świtek A, Błaszczyk I, Bogus K, Łasut- Szyszka B, Krzystanek M, Worthington JJ. Effect of Escitalopram on the Number of DCX-Positive Cells and NMUR2 Receptor Expression in the Rat Hippocampus under the Condition of NPSR Receptor Blockade. Pharmaceuticals (Basel). 2022 May 20;15(5):631. doi: 10.3390/ph15050631. PMID: 35631458; PMCID: PMC9143903. 19: Piwowarczyk-Nowak A, Pałasz A, Suszka-Świtek A, Della Vecchia A, Grajoszek A, Krzystanek M, Worthington JJ. Escitalopram alters local expression of noncanonical stress-related neuropeptides in the rat brain via NPS receptor signaling. Pharmacol Rep. 2022 Aug;74(4):637-653. doi: 10.1007/s43440-022-00374-z. Epub 2022 Jun 2. PMID: 35653031. 20: Li C, Wu XJ, Li W. Neuropeptide S promotes maintenance of newly formed dendritic spines and performance improvement after motor learning in mice. Peptides. 2022 Oct;156:170860. doi: 10.1016/j.peptides.2022.170860. Epub 2022 Aug 12. PMID: 35970276.