AMG-3969

SKU: orb1296239

Description

AMG-3969 is a potent small molecule disruptor of the glucokinase-glucokinase regulatory protein (GK-GKRP) interaction, exhibiting an IC50 of 4 nM. This tool compound is valuable for diabetes research, enabling the study of hepatic glucose metabolism in both cellular and animal models to explore potential therapeutic strategies.

Research Area

Metabolism Research

Key Properties

• CAS Number: 1361224-53-4
• MW: 522.46
• Purity: 99.65% (May vary between batches)
• Formula: C₂₁H₂₀F₆N₄O₃S
• SMILES: CC#C[C@H]1CN(CCN1c1ccc(cc1)C(O)(C(F)(F)F)C(F)(F)F)S(=O)(=O)c1ccc(N)nc1
• Target: Glucokinase
• Solubility: DMSO:100 mg/mL (191.4 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (7.66 mM)

Bioactivity

• Target IC50:
  GK-GKRP:4 nM (cell free)
• In Vivo:
  AMG-3969, at a dosage of 100 mg/kg, significantly lowers blood glucose levels, achieving a 56% reduction eight hours post-administration . This compound effectively normalizes blood glucose levels across various rodent diabetes models and exhibits favorable in vivo pharmacokinetic properties in rats (75%). It also progressively reduces blood glucose levels in db/db mice in a dose-responsive manner . Demonstrating efficacy across three diabetes models—diet-induced obese (DIO), ob/ob, and db/db mice, AMG-3969, however, does not impact blood glucose in normoglycemic C57BL/6 (B6) mice. Additionally, it is highly efficient in enhancing carbohydrate metabolism, leading to noticeable prolonged effects on carbohydrate oxidation, evident from the increased respiratory exchange ratio observed up to the following day post a single administration .
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• In Vitro:
  AMG-3969 demonstrates significant cellular activity (EC50: 0.202 μM; IC50: 4 nM) [1,2], reversing GKRP's inhibitory effect on GK activity and promoting GK translocation in vitro (isolated hepatocytes) .
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• Animal Research:
  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 .
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Glucokinase, GK-GKRP, Hexokinase D, Hexokinase IV, Inhibitor, inhibit, AMG 3969, AMG3969, AMG-3969

Compound Identifiers

PubChem CID

73053709