| Size | Price | Stock | Qty |
|---|---|---|---|
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
AMG-3969 is a potent, novel and metabolically stable disruptor of glucokinase-glucokinase regulatory protein interaction (GK-GKRP) with IC50 of 4 nM. AMG-3969 exhibits potent cellular activity with an EC50 of 0.202 μM and IC50 of 4 nM. It potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation in vitro (isolated hepatocytes). When administered to db/db mice, AMG-3969 demonstrated a robust pharmacodynamic response (GK translocation) as well as statistically significant dose-dependent reductions in fed blood glucose levels. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.
| ln Vitro |
Strong cellular activity is demonstrated by AMG-3969, which has an EC50 of 0.202 μM and an IC50 of 4 nM[1], [2]. In vitro (isolated hepatocytes), it effectively counteracts the inhibitory effect of GKRP on GK activity and stimulates GK translocation[3].
|
||
|---|---|---|---|
| ln Vivo |
According to research, AMG-3969 significantly lowers blood glucose levels in db/db mice in a dose-dependent manner and exhibits good in vivo pharmacokinetic (PK) properties in rats (75%). Blood glucose levels are significantly lowered by AMG-3969 (100 mg/kg), with a strong efficacy (56% reduction) seen at the 8-hour mark[2]. In three diabetes models—diet-induced obese (DIO), ob/ob, and db/db mice—AMG-3969 shows dose-dependent efficacy. In normoglycaemic C57BL/6 (B6) mice, however, AMG-3969 is ineffective in lowering blood glucose. When it comes to promoting carbohydrate substrate, AMG-3969 is very effective. After a single dosage, AMG-3969 shows prolonged changes to carbohydrate oxidation, as evidenced by an increased respiratory exchange ratio into the following day and night[3].
|
||
| Animal Protocol |
|
||
| References |
|
| Molecular Formula |
C21H20F6N4O3S
|
|
|---|---|---|
| Molecular Weight |
522.46
|
|
| Exact Mass |
522.116
|
|
| Elemental Analysis |
C, 48.28; H, 3.86; F, 21.82; N, 10.72; O, 9.19; S, 6.14
|
|
| CAS # |
1361224-53-4
|
|
| Related CAS # |
|
|
| PubChem CID |
73053709
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.6±0.1 g/cm3
|
|
| Boiling Point |
648.8±65.0 °C at 760 mmHg
|
|
| Flash Point |
346.2±34.3 °C
|
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
|
| Index of Refraction |
1.598
|
|
| LogP |
4.51
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
13
|
|
| Rotatable Bond Count |
4
|
|
| Heavy Atom Count |
35
|
|
| Complexity |
901
|
|
| Defined Atom Stereocenter Count |
1
|
|
| SMILES |
CC#C[C@@H]1N(C2=CC=C(C(C(F)(F)F)(O)C(F)(F)F)C=C2)CCN(S(=O)(C3=CN=C(N)C=C3)=O)C1
|
|
| 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
|
|
| Chemical Name |
2-[4-[(2S)-4-(6-aminopyridin-3-yl)sulfonyl-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9140 mL | 9.5701 mL | 19.1402 mL | |
| 5 mM | 0.3828 mL | 1.9140 mL | 3.8280 mL | |
| 10 mM | 0.1914 mL | 0.9570 mL | 1.9140 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA