JMV 2959 HCl is a growth hormone secretagogue receptor type 1a (GHS-R1a) antagonist that acts on LLC-PK1 cells and inhibits GHS-R1a with IC50 of 32±3 nM.

Physicochemical Properties

Molecular Formula	C30H33CLN6O2
Molecular Weight	545.075025320053
Exact Mass	544.235
CAS #	2448414-54-6
Related CAS #	JMV 2959;925238-89-7
PubChem CID	72193865
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	11
Heavy Atom Count	39
Complexity	726
Defined Atom Stereocenter Count	1
SMILES	COC1=CC=C(C=C1)CN2C(=NN=C2[C@@H](CC3=CNC4=CC=CC=C43)NC(=O)CN)CCC5=CC=CC=C5.Cl
InChi Key	QRRDZYKIVMLOJQ-HZPIKELBSA-N
InChi Code	InChI=1S/C30H32N6O2.ClH/c1-38-24-14-11-22(12-15-24)20-36-28(16-13-21-7-3-2-4-8-21)34-35-30(36)27(33-29(37)18-31)17-23-19-32-26-10-6-5-9-25(23)26;/h2-12,14-15,19,27,32H,13,16-18,20,31H2,1H3,(H,33,37);1H/t27-;/m1./s1
Chemical Name	2-amino-N-[(1R)-2-(1H-indol-3-yl)-1-[4-[(4-methoxyphenyl)methyl]-5-(2-phenylethyl)-1,2,4-triazol-3-yl]ethyl]acetamide;hydrochloride
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	IC50: 32±3 nM (GHS-R1a, in LLC-PK1 cells)[1]
ln Vitro	With an IC50 of 32 nM, JMV 2959 is an antagonist of growth hormone secretagogue receptor type 1a (GHS-R1a). By itself, JMV 2959 is unable to cause any intracellular calcium mobilization. The Schild method is used to determine the receptor/JMV 2959 complex's dissociation constant. The dissociation constant Kb, as determined by this experiment, is 19±6 nM[1].
ln Vivo	Ghrelin (0.033, 0.1, and 0.33 mg/kg) administered intraperitoneally (ip) has no effect on rats' prepulse inhibition (PPI) or auditory startle reactions (ASR). On the other hand, dose-dependently increasing PPI and decreasing ASR is seen with intraperitoneal injection of JMV 2959 (1, 3, and 6 mg/kg). While pretreatment with the highest dose of Ghrelin does not potentiate or change PPI responses of a sub-threshold dose of PCP (0.75 mg/kg), pretreatment with JMV 2959 at a level that has no effect on ASR or PPI per se entirely inhibits Phencyclidine (PCP)-induced (2 mg/kg) deficits in PPI[2].
References	[1]. The 1,2,4-triazole as a scaffold for the design of ghrelin receptor ligands: development of JMV 2959, a potent antagonist. Amino Acids. 2013 Feb;44(2):301-14. [2]. Blockade of growth hormone secretagogue receptor 1A signaling by JMV 2959 attenuates the NMDAR antagonist, phencyclidine-induced impairments in prepulse inhibition. Psychopharmacology (Berl). 2015 Dec;232(23):4285-92.

Solubility Data

Solubility (In Vitro)

DMSO: 250 mg/mL (458.65 mM) H2O: 25 mg/mL (45.86 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.82 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 (3.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.82 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. Solubility in Formulation 4: 100 mg/mL (183.46 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8346 mL	9.1730 mL	18.3459 mL
	5 mM	0.3669 mL	1.8346 mL	3.6692 mL
	10 mM	0.1835 mL	0.9173 mL	1.8346 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.