AMG-221
AMG-221, BVT-83370, is a potent and selective 11β-HSD1 inhibitor. AMG-221 decreased fed blood glucose and insulin levels and reduced body weight in diet-induced obesity mice. AMG 221 potently blocked 11β-HSD1 activity, producing sustained inhibition for the 24-hour study duration as measured in ex vivo adipose samples. Early characterization of concentration-response relationships can support rational selection of dose and regimen for future studies.
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Chemical Information
| Name | AMG-221 |
|---|---|
| Iupac Chemical Name | (5S)-2-[[(1R,3S,4S)-3-bicyclo[2.2.1]heptanyl]amino]-5-methyl-5-propan-2-yl-1,3-thiazol-4-one |
| Synonyms | AMG-221; AMG 221; AMG221; BVT-83370; BVT83370; BVT 83370; |
| Molecular Formula | C14H22N2OS |
| Molecular Weight | 266.403 |
| Smile | 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 |
| InChiKey | YCNCXQNUXCHRRX-ZHPDPMBESA-N |
| InChi | O=C1N=C(N[C@H]2C[C@]3([H])CC[C@@]2([H])C3)S[C@@]1(C)C(C)C |
| CAS Number | 1095565-81-3 |
| Related CAS |
Ordering Information
| Packaging | Price | Availability | Purity | Shipping Time |
|---|---|---|---|---|
| Bulk | Enquiry | Enquiry | Enquiry |
| Formulation | Solid powder |
|---|---|
| Purity | 98% Min. |
| Storage | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Solubility | Soluble in DMSO |
| Handling | |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| HS Code |
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| Mechanism | |
| Cell study | |
| Animal study | |
| Clinical study |
1: Gao Q, Kimura RE, Zhang X, Nam J, Amore BM, Hickman D, Greg Slatter J, Emery MG. Intestinal and hepatic first-pass extraction of the 11β-HSD1 inhibitor AMG 221 in rats with chronic vascular catheters. Xenobiotica. 2014 Mar;44(3):264-9. doi: 10.3109/00498254.2013.769074. PubMed PMID: 23517558.
2: Zhu X, Slatter JG, Emery MG, Deane MR, Akrami A, Zhang X, Hickman D, Skiles GL, Subramanian R. Activity-based exposure comparisons among humans and nonclinical safety testing species in an extensively metabolized drug candidate. Xenobiotica. 2013 Jul;43(7):617-27. doi: 10.3109/00498254.2012.747711. PubMed PMID: 23244593.
3: Greene RJ, Davis JA, Subramanian R, Deane MR, Emery MG, Slatter JG. Regiospecific and stereospecific triangulation of the structures of metabolites formed by sequential metabolism at multiple prochiral centers. Drug Metab Dispos. 2012 May;40(5):928-42. doi: 10.1124/dmd.111.043166. PubMed PMID: 22328582.
4: Li A, Yuan CC, Chow D, Chen M, Emery MG, Hale C, Zhang X, Subramanian R, St Jean DJ Jr, Komorowski R, Véniant M, Wang M, Fotsch C. 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. doi: 10.1021/ml2001467. PubMed PMID: 24900270; PubMed Central PMCID: PMC4018091.
5: Gibbs JP, Emery MG, McCaffery I, Smith B, Gibbs MA, Akrami A, Rossi J, Paweletz K, Gastonguay MR, Bautista E, Wang M, Perfetti R, Daniels O. Population pharmacokinetic/pharmacodynamic model of subcutaneous adipose 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity after oral administration of AMG 221, a selective 11β-HSD1 inhibitor. J Clin Pharmacol. 2011 Jun;51(6):830-41. doi: 10.1177/0091270010374470. PubMed PMID: 20663992.
6: Véniant MM, Hale C, Hungate RW, Gahm K, Emery MG, Jona J, Joseph S, Adams J, Hague A, Moniz G, Zhang J, Bartberger MD, Li V, Syed R, Jordan S, Komorowski R, Chen MM, Cupples R, Kim KW, St Jean DJ Jr, Johansson L, Henriksson MA, Williams M, Vallgårda J, Fotsch C, Wang M. 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(5 H)-one (AMG 221). J Med Chem. 2010 Jun 10;53(11):4481-7. doi: 10.1021/jm100242d. PubMed PMID: 20465278.
7: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Dec;31(10):661-700. PubMed PMID: 20140276.
8: Caille S, Cui S, Hwang TL, Wang X, Faul MM. Two asymmetric syntheses of AMG 221, an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1. J Org Chem. 2009 May 15;74(10):3833-42. doi: 10.1021/jo900287b. PubMed PMID: 19391575.
Chemical Structure
