| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 50mg | |||
| Other Sizes |
| Targets |
GPR40 (FFA1) – EC₅₀ (aequorin assay, buffer with 0.01% HSA) = 36 ± 10 nM; EC₅₀ (IP₃ accumulation assay, 0.3% human serum) = 3.6 nM.
Insulin secretion in isolated islets from hGPR40 knock‑in mice – EC₅₀ = 55 nM (in 16.7 mM glucose, 0.1% HSA). |
|---|---|
| ln Vitro |
(1) In aequorin assay using CHO cells stably transfected with human GPR40, AM‑4668 showed EC₅₀ = 36 ± 10 nM. [1]
(2) In inositol phosphate (IP₃) accumulation assay using A9 cells expressing human GPR40, AM‑4668 gave EC₅₀ = 3.6 nM. [1] (3) In isolated pancreatic islets from human GPR40 knock‑in mice, AM‑4668 stimulated insulin secretion with EC₅₀ = 55 nM (in buffer containing 16.7 mM glucose and 0.1% human serum albumin). [1] (4) AM‑4668 showed no inhibition of hERG channel (IC₅₀ not reported, >30 µM implied) and demonstrated low potential for CYP inhibition and induction (no specific IC₅₀ values given). [1] |
| ln Vivo |
In an oral glucose tolerance test (OGTT) in female human GPR40 knock‑in mice (28 weeks old), oral administration of AM‑4668 at 10 mg/kg (formulated in 1% methylcellulose and 1% Tween‑80) 1 h before glucose challenge (2 g/kg glucose) significantly reduced blood glucose levels. The glucose AUC in treated animals was 19% lower than in vehicle‑treated controls. [1]
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| Enzyme Assay |
The aequorin assay measured GPR40 activation in CHO cells stably transfected with human GPR40, using aequorin as a calcium indicator; assay buffer contained 0.01% human serum albumin. The inositol phosphate accumulation assay used A9 cells stably expressing human GPR40, with 0.3% human serum, and measured IP₁ accumulation. Detailed protocols are referenced from prior publications (refs 14 and 15). No direct enzyme kinetic or binding experiments were described. [1]
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| Cell Assay |
(1) Aequorin assay: CHO cells expressing human GPR40 were treated with compounds, and calcium mobilization was measured via aequorin luminescence; EC₅₀ values determined. [1]
(2) IP₃ accumulation assay: A9 cells expressing human GPR40 were treated with compounds, and IP₁ accumulation was quantified; EC₅₀ values determined. [1] (3) Insulin secretion assay: Islets isolated from human GPR40 knock‑in mice were incubated with AM‑4668 in buffer containing 16.7 mM glucose and 0.1% human serum albumin; insulin release was measured to determine EC₅₀. [1] |
| Animal Protocol |
Female human GPR40 knock‑in mice (28 weeks old) were fasted for 6 h, then dosed orally with AM‑4668 at 10 mg/kg in 1% methylcellulose and 1% Tween‑80. One hour later, an oral glucose challenge (2 g/kg glucose) was administered. Blood glucose was measured from tail vein samples at various time points using a blood glucose monitoring system. [1]
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| ADME/Pharmacokinetics |
Rat: CL = 0.09 L/h/kg, t₁/₂ = 5.3 h, Vdss = 0.68 L/kg, oral F = 77%.
Dog: CL = 0.15 L/h/kg, t₁/₂ = 5.6 h, Vdss = 0.60 L/kg, oral F = 100%. Cynomolgus monkey: CL = 0.04 L/h/kg, t₁/₂ = 14 h, Vdss = 0.35 L/kg, oral F = 65%. Brain‑to‑plasma ratio in rat at 3 h after a 5 mg/kg oral dose was 0.02, indicating low CNS penetration. [1] |
| Toxicity/Toxicokinetics |
AM‑4668 showed no inhibition of hERG channel (IC₅₀ > 30 µM, no exact value reported) and exhibited low potential for drug‑drug interactions based on CYP inhibition and induction assays (no specific IC₅₀ or fold‑induction values provided). No other toxicity data (e.g., LD₅₀, organ toxicity) are reported. [1]
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| References | |
| Additional Infomation |
AM‑4668 (compound 10) is an isoxazole derivative with a polar surface area of 85.5 Ų (vs. 46.5 Ų for AMG 837). It was synthesized via Michael addition, nitrile oxide formation, deprotection, alkylation, and hydrolysis (Scheme 1). It is a potent GPR40 agonist with excellent PK properties across species and efficacy in an OGTT model. The compound was designed to avoid CNS exposure while retaining peripheral insulin‑secretagogue activity. No clinical trial or FDA approval status is mentioned. [1]
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| Molecular Formula |
C24H19F3N2O4S
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|---|---|
| Molecular Weight |
488.48
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| Exact Mass |
488.101
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| CAS # |
1011531-27-3
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| PubChem CID |
24897670
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
633.4±65.0 °C at 760 mmHg
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| Flash Point |
336.9±34.3 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.583
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| LogP |
5.27
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
669
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(SC(=N1)C2=CC=C(C=C2)C(F)(F)F)COC3=CC=C(C=C3)[C@H](CC(=O)O)C4=NOC=C4
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| InChi Key |
BMLGZNVPWRUVNM-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C24H19F3N2O4S/c1-14-21(34-23(28-14)16-2-6-17(7-3-16)24(25,26)27)13-32-18-8-4-15(5-9-18)19(12-22(30)31)20-10-11-33-29-20/h2-11,19H,12-13H2,1H3,(H,30,31)/t19-/m0/s1
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| Chemical Name |
(3S)-3-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]phenyl]-3-(1,2-oxazol-3-yl)propanoic acid
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| Synonyms |
AM 4668 AM4668AM-4668
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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 | 2.0472 mL | 10.2358 mL | 20.4717 mL | |
| 5 mM | 0.4094 mL | 2.0472 mL | 4.0943 mL | |
| 10 mM | 0.2047 mL | 1.0236 mL | 2.0472 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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