| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
AMG-1694 targets the interaction between glucokinase (GK) and glucokinase regulatory protein (GKRP). GK is a key enzyme in glucose metabolism that catalyzes the phosphorylation of glucose to glucose-6-phosphate, serving as the glucose sensor in pancreatic beta-cells and hepatocytes. GKRP is an inhibitor of GK that binds to GK and inhibits its activity. By disrupting the GK-GKRP interaction with an IC50 of 7 nM, AMG-1694 promotes the dissociation of the GK-GKRP complex and indirectly increases GK enzyme activity. This leads to enhanced glucose sensing and increased glucose utilization. AMG-1694 can normalize blood glucose levels in several rodent models of diabetes.
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| ln Vitro |
In the presence of GKRP, AMG-1694 may very effectively restore the enzymatic activity of GK, with an EC50 of 0.020 μM [1].
AMG-1694 demonstrates potent in vitro activity as a GK-GKRP disruptor. The compound promotes the dissociation of the GK-GKRP complex with an IC50 of 7 nM. By disrupting the GK-GKRP interaction, AMG-1694 indirectly increases GK enzyme activity. The compound's activity is concentration-dependent, with potent effects observed at nanomolar concentrations. AMG-1694 is a preclinical research tool used to increase glucokinase activity and investigate glucose metabolism. Its potency and selectivity for the GK-GKRP interaction make it a valuable tool for studying glucose homeostasis and diabetes. |
| ln Vivo |
In vivo, AMG-1694 has demonstrated significant efficacy in rodent models of diabetes. The compound can normalize blood glucose levels in several rodent models of diabetes. AMG-1694 lowers blood glucose in diabetic but not normoglycemic animals. This glucose-lowering effect is consistent with the compound's mechanism of action as a GK-GKRP disruptor that increases GK activity. AMG-1694 effectively reverses GKRP-mediated inhibition of GK activity. The compound's in vivo efficacy has been characterized in various diabetic models. Its oral bioavailability makes it suitable for convenient dosing in research settings. Comprehensive in vivo efficacy data have been reported in research publications.
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| Enzyme Assay |
In vitro binding assays for AMG-1694 involve measuring the disruption of the GK-GKRP interaction. Purified GK and GKRP proteins are incubated with varying concentrations of the test compound, and the interaction is measured using surface plasmon resonance (SPR), fluorescence polarization, or AlphaScreen technology. IC50 values are calculated from dose-response curves using non-linear regression analysis. The compound has an IC50 of 7 nM for promoting dissociation of the GK-GKRP complex. Alternatively, GK enzyme activity assays can be performed in the presence of GKRP and varying concentrations of the compound to measure the relief of GKRP-mediated inhibition of GK activity. Each concentration is typically tested in duplicate or triplicate with appropriate positive and negative controls.
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| Cell Assay |
In vitro cellular assays for AMG-1694 are performed using hepatocytes or pancreatic beta-cells. Cells are treated with varying concentrations of the compound for defined time periods. GK activity is measured in cell lysates using a glucose phosphorylation assay. Glucose metabolism is assessed by measuring glucose consumption or lactate production. In pancreatic beta-cells, glucose-stimulated insulin secretion can be measured by ELISA. In hepatocytes, glycogen synthesis can be assessed by measuring [14C]-glucose incorporation into glycogen. Signaling pathway activation is assessed by Western blot for phosphorylated signaling intermediates. Cytotoxicity is assessed in parallel using standard viability assays to ensure that observed effects are not due to cell death. EC50 values for stimulation of GK activity or glucose metabolism are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal studies for AMG-1694 are conducted using rodent models of diabetes, such as db/db mice, ob/ob mice, or high-fat diet-induced obese mice. The compound is administered via oral gavage at various doses and schedules. Blood glucose levels are measured at various time points after administration. Oral glucose tolerance tests (OGTT) are performed by administering a glucose load and measuring blood glucose levels over time. Insulin levels are measured in serum samples to assess insulin secretion. Pharmacokinetic studies assess drug concentrations in plasma. Body weight and food intake are monitored as safety indicators. Efficacy is expressed as reduction in blood glucose and improvement in glucose tolerance compared to vehicle-treated controls.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of AMG-1694 have been characterized in preclinical studies. The compound has a molecular formula of C23H30F3N3O4S2 and a molecular weight of 533.63 g/mol. Its IUPAC name is 1,1,1-trifluoro-2-(4-((S)-2-(morpholinomethyl)-4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)propan-2-ol. AMG-1694 is orally bioavailable. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and oral bioavailability have been characterized in animal models. The compound's pharmacokinetic profile supports its use in preclinical studies of diabetes and glucose metabolism.
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| Toxicity/Toxicokinetics |
AMG-1694 is intended for laboratory research use only and has not undergone comprehensive clinical toxicology testing. As a GK-GKRP disruptor that increases GK activity, the compound would be expected to have effects on glucose metabolism. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has been conducted as part of preclinical development. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
AMG-1694 is a potent GK-GKRP disruptor with an IC50 of 7 nM. It promotes dissociation of the GK-GKRP complex and indirectly increases GK activity. AMG-1694 normalizes blood glucose in rodent diabetes models and lowers glucose in diabetic but not normoglycemic animals. The compound has a molecular formula of C23H30F3N3O4S2 and a molecular weight of 533.63 g/mol. AMG-1694 has not entered clinical trials and is available for research purposes only.
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| Molecular Formula |
C22H28F3N3O4S2
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|---|---|
| Molecular Weight |
519.600633621216
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| Exact Mass |
533.162
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| CAS # |
1361217-07-3
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| PubChem CID |
66582747
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
820
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| Defined Atom Stereocenter Count |
3
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| SMILES |
S(C1=CC=CS1)(N1CCN(C2C=CC(C(C)(C(F)(F)F)O)=CC=2)[C@@H](CN2CCOCC2)C1)(=O)=O
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| InChi Key |
OJTJLEFGCNYTBQ-RBDMOPTHSA-N
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| InChi Code |
InChI=1S/C23H30F3N3O4S2/c1-17-16-33-12-11-27(17)14-20-15-28(35(31,32)21-4-3-13-34-21)9-10-29(20)19-7-5-18(6-8-19)22(2,30)23(24,25)26/h3-8,13,17,20,30H,9-12,14-16H2,1-2H3/t17-,20-,22+/m0/s1
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| Chemical Name |
(2R)-1,1,1-trifluoro-2-[4-[(2S)-2-[[(3S)-3-methylmorpholin-4-yl]methyl]-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9246 mL | 9.6228 mL | 19.2456 mL | |
| 5 mM | 0.3849 mL | 1.9246 mL | 3.8491 mL | |
| 10 mM | 0.1925 mL | 0.9623 mL | 1.9246 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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