WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 530955
Description: 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.
MedKoo Cat#: 530955
Chemical Formula: C21H20F6N4O3S
Exact Mass: 522.116
Molecular Weight: 522.4664
Elemental Analysis: C, 48.28; H, 3.86; F, 21.82; N, 10.72; O, 9.19; S, 6.14
Synonym: AMG-3969; AMG 3969; AMG3969.
IUPAC/Chemical Name: 2-(4-((2S)-4-((6-amino-3-pyridinyl)sulphonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol
InChi Key: SIFKNECWLVONIH-INIZCTEOSA-N
InChi Code: InChI=1S/C21H20F6N4O3S/c1-2-3-16-13-30(35(33,34)17-8-9-18(28)29-12-17)10-11-31(16)15-6-4-14(5-7-15)19(32,20(22,23)24)21(25,26)27/h4-9,12,16,32H,10-11,13H2,1H3,(H2,28,29)/t16-/m0/s1
SMILES Code: OC(C(F)(F)F)(C1=CC=C(N2[C@@H](C#CC)CN(S(=O)(C3=CC=C(N)N=C3)=O)CC2)C=C1)C(F)(F)F
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
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.
Storage Condition: 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
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 522.4664 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
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, Zhang J, Liu L, Norman MH, Andrews KL, Bartberger MD, Van G, Galbreath EJ, Vonderfecht SL, Wang M, Jordan SR, Véniant MM, Hale C. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature. 2013 Dec 19;504(7480):437-40. doi: 10.1038/nature12724. Epub 2013 Nov 13. PubMed PMID: 24226772.
Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus.