AMG-3969
AMG-3969
CAS: 1361224-53-4
Molecular Formula: C21H20F6N4O3S
AMG-3969 - Names and Identifiers
AMG-3969 - Physico-chemical Properties
| Molecular Formula | C21H20F6N4O3S |
| Molar Mass | 522.46 |
| Density | 1.56±0.1 g/cm3(Predicted) |
| Boling Point | 648.8±65.0 °C(Predicted) |
| Solubility | Soluble in DMSO |
| pKa | 10.12±0.15(Predicted) |
| Storage Condition | 2-8°C(protect from light) |
| Use | AMG-3969 is a GK-GKRP disruptor. AMG-3969 normalized blood glucose levels in several rodent models of diabetes. AMG-3969 potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). AMG-3969 blood glucose lowering was restricted to diabetic and not normoglycaemic animals. |
| In vitro study | AMG-3969 exhibits potent cellular activity with an EC 50 of 0.202 μM and IC 50 of 4 nM, . It potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation in vitro (isolated hepatocytes). |
| In vivo study | AMG-3969 has good in vivo pharmacokinetic (PK) properties in rats (75%) and significantly lowers blood glucose levels in a dose-dependent manner db/db mice. AMG-3969 (100 mg/kg) demonstrates significant reductions in blood glucose with robust efficacy (56% reduction) observed at the 8 h time point. AMG-3969 demonstrates dose-dependent efficacy in three models of diabetes: diet induced obese (DIO), ob/ob and db/db mice; however,AMG-3969 is ineffective in lowering blood glucose in normoglycaemic C57BL/6 (B6) mice. AMG-3969 is highly effective in promoting carbohydrate substrate. AMG-3969 exhibits extended changes to carbohydrate oxidation as observed by increased respiratory exchange ratio into the next night and day after a single dose. |
AMG-3969 - Reference
| Reference Show more | 1: Bourbeau MP, Ashton KS, Yan J, St Jean DJ Jr. Nonracemic synthesis of GK-GKRP disruptor AMG-3969. J Org Chem. 2014 Apr 18;79(8):3684-7. doi: 10.1021/jo500336e. Epub 2014 Apr 10. PubMed PMID: 24678849. 2: Nishimura N, Norman MH, Liu L, Yang KC, Ashton KS, Bartberger MD, Chmait S, Chen J, Cupples R, Fotsch C, Helmering J, Jordan SR, Kunz RK, Pennington LD, Poon SF, Siegmund A, Sivits G, Lloyd DJ, Hale C, St Jean DJ Jr. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N'-arylpiperazine series. J Med Chem. 2014 Apr 10;57(7):3094-116. doi: 10.1021/jm5000497. Epub 2014 Mar 31. PubMed PMID: 24611879. 3: St Jean DJ Jr, Ashton KS, Bartberger MD, Chen J, Chmait S, Cupples R, Galbreath E, Helmering J, Hong FT, Jordan SR, Liu L, Kunz RK, Michelsen K, Nishimura N, Pennington LD, Poon SF, Reid D, Sivits G, Stec MM, Tadesse S, Tamayo N, Van G, Yang KC, Zhang J, Norman MH, Fotsch C, Lloyd DJ, Hale C. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles. J Med Chem. 2014 Jan 23;57(2):325-38. doi: 10.1021/jm4016747. Epub 2014 Jan 9. PubMed PMID: 24405213. 4: Lloyd DJ, St Jean DJ Jr, Kurzeja RJ, Wahl RC, Michelsen K, Cupples R, Chen M, Wu J, Sivits G, Helmering J, Komorowski R, Ashton KS, Pennington LD, Fotsch C, Vazir M, Chen K, Chmait S, |
AMG-3969 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 1.914 ml | 9.57 ml | 19.14 ml |
| 5 mM | 0.383 ml | 1.914 ml | 3.828 ml |
| 10 mM | 0.191 ml | 0.957 ml | 1.914 ml |
| 5 mM | 0.038 ml | 0.191 ml | 0.383 ml |
Last Update：2024-01-02 23:10:35
AMG-3969 - Animal Experiment
Diabetic db/db mice are used in the study. At 8:00 AM, mice are bled via retro-orbital sinus puncture and blood glucose values are determined and used to randomize the animals in which their averages are similar, and only mice with blood glucose ranges between 300 and 500 mg/dL are included. Vehicle (2% hydroxypropyl methylcellulose, 1% Tween 80, pH 2.2 adjusted with MSA) or AMG-3969 (10, 30, 100 mg/kg) are gavaged at 9:00 AM. Blood glucose is measured at 4, 6, or 8 h posttreatment. At each time point, a 15 μL sample of whole blood is analyzed for drug exposure .
Last Update：2023-08-16 21:32:38
Supplier List
Spot supply
Product Name: AMG-3969 Visit Supplier Webpage Request for quotationCAS: 1361224-53-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
Spot supply
Product Name: AMG-3969 Visit Supplier Webpage Request for quotationCAS: 1361224-53-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
View History