BMS-604992 (EX-1314) di-HCl is a selective, orally bioactive, small molecule growth hormone secretagogue receptor (GHSR) agonist. BMS-604992 di-HCl has high affinity (ki=2.3 nM) and strong functional activity (EC50=0.4 nM). BMS-604992 di-HCl stimulates feeding in rodents.

Physicochemical Properties

Molecular Formula	C24H33CL2N7O5
Molecular Weight	570.47
Exact Mass	569.192
CAS #	1469750-46-6
Related CAS #	BMS-604992;674343-47-6;BMS-604992 free base;760944-56-7
PubChem CID	131888685
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	12
Heavy Atom Count	38
Complexity	761
Defined Atom Stereocenter Count	1
SMILES	CC(C)(C(=O)N[C@H](COCC1=CC=CC=C1)C2=NN=C3N2C(=CC=C3)COC(=O)N(C)CC(=O)N)N.Cl.Cl
InChi Key	LYVQQKKDBUZUGQ-JPKZNVRTSA-N
InChi Code	InChI=1S/C24H31N7O5.2ClH/c1-24(2,26)22(33)27-18(15-35-13-16-8-5-4-6-9-16)21-29-28-20-11-7-10-17(31(20)21)14-36-23(34)30(3)12-19(25)32;;/h4-11,18H,12-15,26H2,1-3H3,(H2,25,32)(H,27,33);2*1H/t18-;;/m1../s1
Chemical Name	[3-[(1S)-1-[(2-amino-2-methylpropanoyl)amino]-2-phenylmethoxyethyl]-[1,2,4]triazolo[4,3-a]pyridin-5-yl]methyl N-(2-amino-2-oxoethyl)-N-methylcarbamate;dihydrochloride
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	EC50: 0.4 nM (GHSR), Ki: 2.3 nM (GHSR)[1]
ln Vitro	BMS-604992 demonstrates strong functional activity (EC50=0.4 nM) and high-affinity binding (Ki=2.3 nM) for the ghrelin receptor[1].
ln Vivo	In comparison to mice given with vehicle, BMS-604992 (500 μg/kg; ip; 5 minutes) significantly increases stomach emptying[1]. With a minimum effective dose of roughly 10 mg/kg, BMS-604992 (1~1000 mg/kg; po; 1 hour) elicits a dose-responsive increase in food intake in comparison to vehicle-treated controls and exhibits a dose-linear increase in plasma concentrations at the 1-hour time point[1]. At the 5-minute mark, BMS-604992 (300 mg/kg; po; 5~20 minutes) significantly alters the situation[1]. Compared to vehicle-treated controls, BMS-604992 (500 μg/kg; ip; 4 hours) increases food intake by around two times[1].
Animal Protocol	Animal/Disease Models: C57BL/6 mice Doses: 500 μg/kg Route of Administration: Ip; 5 minutes Experimental Results: Resulted in a significant increase in gastric emptying compared with vehicle-treated mice. Animal/Disease Models: C57BL/6 mice Doses: 1~1000 mg/kg Route of Administration: Po; 1 hour Experimental Results: demonstrated a dose-linear increase in plasma concentrations at the 1 hour time point and elicited a dose-responsive increase in food intake relative to vehicle-treated controls, with a minimum effective dose of approximately 10 mg/kg. Animal/Disease Models: SD rat Doses: 300 mg/kg Route of Administration: Po; 5~20 minutes Experimental Results: Observed a significant difference at the 5 minutes time point. Animal/Disease Models: Male GhrR KO and WT mice Doses: 500 μg/kg Route of Administration: Ip; 4 hrs (hours) Experimental Results: Increased food intake approximately 2-fold compared with vehicle-treated controls.
References	[1]. Enhanced gastrointestinal motility with orally active ghrelin receptor agonists. J Pharmacol Exp Ther. 2009;329(3):1178-1186.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7529 mL	8.7647 mL	17.5294 mL
	5 mM	0.3506 mL	1.7529 mL	3.5059 mL
	10 mM	0.1753 mL	0.8765 mL	1.7529 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.