AZD1979 is a novel and potent antagonist of Melanin-concentrating hormone receptor 1 (MCHr1) with an IC50 of ~12 nM. AZD1979 affects both food intake and energy expenditure. AZD1979 also lowers body weight in a species expressing both MCH receptors holds promise for the use of MCH1 receptor antagonists for the treatment of human obesity. AZD1979 bound to MCH1 receptors in the CNS and dose-dependently reduced body weight in DIO mice leading to improved homeostasis model assessment-index of insulin sensitivity. AZD1979 did not affect food intake or body weight in Mchr1 KO mice demonstrating specificity for the MCH1 receptor mechanism. In DIO mice, initial AZD1979-mediated body weight loss was driven by decreased food intake, but an additional component of preserved energy expenditure was apparent in pair-feeding and indirect calorimetry studies. AZD1979 also dose-dependently reduced body weight in dogs.

Physicochemical Properties

Molecular Formula	C25H26N4O5
Molecular Weight	462.497745990753
Exact Mass	462.19
CAS #	1254035-84-1
PubChem CID	49801838
Appearance	Off-white to light yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	636.6±65.0 °C at 760 mmHg
Flash Point	338.8±34.3 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.668
LogP	5.01
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	34
Complexity	706
Defined Atom Stereocenter Count	0
InChi Key	BKKPIQPFRAPEAY-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H26N4O5/c1-31-19-8-4-18(5-9-19)22-26-27-23(34-22)24(30)29-11-21(12-29)33-20-6-2-17(3-7-20)10-28-13-25(14-28)15-32-16-25/h2-9,21H,10-16H2,1H3
Chemical Name	(3-(4-((2-oxa-6-azaspiro[3.3]heptan-6-yl)methyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone
Synonyms	AZD1979; AZD-1979; AZD 1979.
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

ln Vivo	Reduced food intake was initially the primary cause of AZD1979-mediated weight loss in DIO mice, however pair-feeding and indirect calorimetry investigations revealed additional mechanism sustaining energy expenditure. In dogs, AZD1979 also decreases body weight in a dose-dependent manner [1].
References	[1]. Effects of a novel potent melanin-concentrating hormone receptor 1 antagonist, AZD1979, on body weight homeostasis in mice and dogs. Br J Pharmacol. 2016 Sep;173(18):2739-51.
Additional Infomation	AZD1979 is a carboxamide resulting from the formal condensation of the carboxy group of 5-(p-methoxyphenyl)-1,3,4-oxadiazole-2-carboxylic acid with the amino group of 3-phenoxyazetidine and in which the phenoxy group has been substituted at the para- position by a 2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl group. It is a melanin concentrating hormone receptor 1 (MCHr1) antagonist. It has a role as a melanin-concentrating hormone receptor antagonist. It is an azaspiro compound, an oxaspiro compound, an oxadiazole, a N-acylazetidine, a member of oxetanes, an aromatic ether and a carboxamide. It is a conjugate base of an AZD1979(1+).

Solubility Data

Solubility (In Vitro)

DMSO : ~33.33 mg/mL (~72.06 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.41 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 25.0 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: ≥ 2.5 mg/mL (5.41 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 25.0 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: ≥ 2.5 mg/mL (5.41 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 25.0 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	2.1622 mL	10.8108 mL	21.6216 mL
	5 mM	0.4324 mL	2.1622 mL	4.3243 mL
	10 mM	0.2162 mL	1.0811 mL	2.1622 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.