SHA 68 (SHA-68, SHA68) is a novel, highly potent and selective non-peptide neuropeptide S receptor (NPSR) antagonist with IC50s of 22.0 and 23.8 nM for NPSR Asn107 and NPSR Ile107, respectively. It has been observed that SHA 68 reduces neuralgia activity and blood-brain barrier (BBB) penetration.

Physicochemical Properties

Molecular Formula	C26H24FN3O3
Molecular Weight	445.485469818115
Exact Mass	445.18
Elemental Analysis	C, 70.10; H, 5.43; F, 4.26; N, 9.43; O, 10.77
CAS #	847553-89-3
PubChem CID	11374217
Appearance	White to off-white solid powder
LogP	4.382
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	33
Complexity	681
Defined Atom Stereocenter Count	0
SMILES	O=C1N2CCN(CC2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1)C(NCC1C=CC(F)=CC=1)=O
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)
Chemical Name	N-[(4-fluorophenyl)methyl]-3-oxo-1,1-diphenyl-5,6,8,8a-tetrahydro-[1,3]oxazolo[3,4-a]pyrazine-7-carboxamide
Synonyms	SHA68; SHA-68; SHA 68
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Asn107 ( IC50 = 22 nM ); Ile107 ( IC50 = 23.8 nM )
ln Vivo	SHA 68 (i.p.; 5 and 50 mg/kg) reduces vertical rearing and climbing as well as horizontal activity induced by NPS[1]. SHA 68 (i.v.; 1 mg/kg) possesses a Vss of 2.53 L/kg, a CL of 4.29 mL/min/kg, and a T1/2 of 0.74 hours[1]. SHA 68 (i.p.; 2.5 mg/kg) has a CL of 4.56 mL/min/kg and a T1/2 of 0.43 hours[1].
Animal Protocol	Male C57BL/6 mice age 8-12 weeks 5 and 50 mg/kg i.p.
References	[1]. 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. [2]. Neuropeptide S increases motor activity and thermogenesis in the rat through sympathetic activation.Neuropeptides. 2017 Oct;65:21-27.

Solubility Data

Solubility (In Vitro)

DMSO: ~250 mg/mL (~561.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2447 mL	11.2236 mL	22.4472 mL
	5 mM	0.4489 mL	2.2447 mL	4.4894 mL
	10 mM	0.2245 mL	1.1224 mL	2.2447 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.