AMG-221 is an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor (antagonist) with Ki of 12.8 nM and IC50 of 10.1 nM. AMG-221 may be utilized in research on type 2 diabetes.

Physicochemical Properties

Molecular Formula	C14H22N2OS
Molecular Weight	266.40228
Exact Mass	266.145
CAS #	1095565-81-3
PubChem CID	135565424
Appearance	Typically exists as solid at room temperature
LogP	3.084
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	18
Complexity	407
Defined Atom Stereocenter Count	4
SMILES	CC(C)C1(C(O)=N/C(=N\C2C3CCC(C3)C2)/S1)C
InChi Key	YCNCXQNUXCHRRX-ZHPDPMBESA-N
InChi Code	InChI=1S/C14H22N2OS/c1-8(2)14(3)12(17)16-13(18-14)15-11-7-9-4-5-10(11)6-9/h8-11H,4-7H2,1-3H3,(H,15,16,17)/t9-,10+,11+,14+/m1/s1
Chemical Name	(5S)-2-[[(1S,2S,4R)-2-bicyclo[2.2.1]heptanyl]imino]-5-methyl-5-propan-2-yl-1,3-thiazolidin-4-one
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 Vitro	Selectivity for the glucocorticoid receptor (GR) and 11β-HSD2 and 17β-HSD1 is demonstrated by AMG-221 (IC50 values > 10 μM for all experiments) [2].
ln Vivo	AMG-221 (25 or 50 mg/kg; bid; oral gavage) decreases 11β-HSD1 activity in DIO mice. At the end of the research, postprandial blood glucose revealed a statistically significant drop compared to the vehicle group. On day 14 and after 12 hours of fasting, glucose tolerance was slightly improved in the AMG-221-treated group compared with the vehicle group [2]. 4 hours after oral administration of AMG-221 at 5, 15 and 50 mg/kg, 11β-HSD1 activity in inguinal fat was decreased by 33%, 55% and 47%, respectively. At 8 hours, 11β-HSD1 activity in inguinal fat in the 5 mg/kg group had reverted to levels near to those in control animals treated with vehicle (~10% inhibition), but considerable inhibition remained. 15 and 50 mg/kg groups (36% and 39% inhibition, respectively) [2]. AMG-221 has high bioavailability in mice, rats and dogs. However, bioavailability in monkeys is minimal [2]. AMG-221 displays modest oral bioavailability (31% in male CD1 mice) upon oral treatment (10 mg/kg) [3]. AMG-221 demonstrates a terminal elimination half-life (male CD1 mice) due to high plasma clearance (3.31 L/h/kg) and large volume of distribution (0.9 L/kg) following intravenous injection (2 mg/kg) 3.32 h) [3].
Animal Protocol	Animal/Disease Models: Diet-Induced Obesity (DIO) Mice [2] Doses: 25 or 50 mg/kg (prepared in 0.1% Tween-80 and 0.5% CMC water) Route of Administration: po (oral gavage); twice (two times) daily for 13 or 14-day Experimental Results: All treatment groups experienced statistically significant decreases in insulin levels compared to the vehicle control group on day 13.
References	[1]. Two asymmetric syntheses of AMG 221, an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1.J Org Chem. 2009 May 15;74(10):3833-42. [2]. Discovery of a potent, orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: identification of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). J Med Chem. 2010 Jun 10;53(11):4481-7. [3]. Synthesis and Evaluation of the Metabolites of AMG 221, a Clinical Candidate for the Treatment of Type 2 Diabetes. ACS Med Chem Lett. 2011 Sep 13;2(11):824-7.

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	3.7538 mL	18.7688 mL	37.5375 mL
	5 mM	0.7508 mL	3.7538 mL	7.5075 mL
	10 mM	0.3754 mL	1.8769 mL	3.7538 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.