AMG-221 

AMG-221 is an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) with a K_i of 12.8 nM in vitro biochemical scintillation proximity assay (SPA) and an IC₅₀ of 10.1 nM in cell-based assays^[1][2]. AMG-221 can be used for the research of type 2 diabetes^[3].

AMG-221 shows selectivity over 11β-HSD2, 17β-HSD1, and glucocorticoid receptor (GR) (IC₅₀ values for all assays are >10 μM)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AMG-221 (25 or 50 mg/kg; b.i.d.; orally gavaged) inhibits 11β-HSD1 activity in DIO mice. At the end of the study, fed blood glucose shows statistically significant reduction in comparison to the vehicle group. On day 14 and after a 12 h fast, glucose tolerance is slightly improved in the AMG-221 treatment groups compared with the vehicle group^[2].
11β-HSD1 activity is inhibited by 33%, 55%, and 47% in the inguinal fat at 4 h after AMG-221 is orally gavaged at 5, 15, and 50 mg/kg, respectively. At 8 h, the 11β-HSD1 activity in the inguinal fat of the 5 mg/kg group has returned to a level (～10% inhibition) close to that in the control animals treated with vehicle, but there is still significant inhibition in the 15 and 50 mg/kg groups (36% and 39% inhibition, respectively)^[2].
AMG-221 has a good bioavailability in mouse, rat, and dog. However, the bioavailability in monkey is low^[2].
AMG-221 exhibits moderate oral bioavailability (male CD1 mouse 31%) following oral administration (10 mg/kg)^[3].
AMG-221 exhibits terminal elimination half-life (male CD1 mouse 3.32 h) due to high plasma clearance (3.31 L/h/kg) combined with large volumes of distribution (0.9 L/kg) following intravenous administration (2 mg/kg)^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

266.40

C₁₄H₂₂N₂OS

1095565-81-3

O=C1N=C(N[C@@H]2[C@@](C3)([H])CC[C@@]3([H])C2)S[C@@]1(C)C(C)C

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Seb Caille, et al. Two asymmetric syntheses of AMG 221, an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1.J Org Chem. 2009 May 15;74(10):3833-42.  [Content Brief]

  [2]. Murielle M Véniant, et al. 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.  [Content Brief]

  [3]. Aiwen Li, et al. 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.  [Content Brief]