| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Firuglipel targets GPR119, a G protein-coupled receptor expressed in pancreatic β-cells and intestinal L-cells. Activation of GPR119 by Firuglipel upregulates glucagon-like peptide-1 (GLP-1) and enhances glucose-dependent insulin secretion. The compound shows high selectivity for GPR119 with an EC50 of 51.5 nM and no significant activity against a panel of 66 other receptors, channels, or transporters.
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| ln Vitro |
In Chinese Hamster Ovary (CHO)-K1 cells expressing human, rat, and mouse GPR119, firuglipel (DS-8500a) increases intracellular cAMP in a concentration-dependent manner with EC50 values of 51.5, 98.4, and 108.1 nM, respectively. In pcDNA3.1/CHO-K1 cells, DS-8500a had no effect on intracellular cAMP [1].
In vitro, Firuglipel demonstrates potent agonism at human GPR119 with an EC50 of 51.5 nM in CHO-K1 cells expressing the receptor. It enhances glucose-stimulated insulin secretion in isolated pancreatic islets and promotes GLP-1 secretion in intestinal L-cells. The compound displays excellent selectivity, showing no significant effects on 66 other receptors, channels, or transporters. These properties support its role as a glucose-dependent insulin secretagogue. |
| ln Vivo |
In type 2 diabetic rats, firuglipel (DS-8500a) (1–30 mg/kg) increases glucose-dependent insulin production, upregulates glucagon-like peptide-1, and improves glucose homeostasis [1].
In vivo, Firuglipel (1-30 mg/kg) upregulates glucagon-like peptide-1 and enhances glucose-dependent insulin secretion in type 2 diabetic rat models. It improves glucose homeostasis and preserves β-cell function in rodent models of type 2 diabetes. The compound prevents increases in glycohemoglobin concentrations in diabetic animal models. Firuglipel is orally available and has been evaluated in preclinical diabetes models. |
| Enzyme Assay |
Not specifically documented for Firuglipel. For GPR119 agonists, typical cell-free binding assays involve radioligand displacement studies using membrane preparations from cells expressing the receptor. Competition binding assays measure the ability of the compound to displace a labeled reference ligand from GPR119. Such assays determine binding affinity (Ki) and confirm target engagement at the receptor level.
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| Cell Assay |
In vitro cellular assays for Firuglipel typically use CHO-K1 cells stably expressing human GPR119. Functional activity is assessed via cAMP accumulation assays, as GPR119 is a Gs-coupled receptor that increases intracellular cAMP upon activation. EC50 values are determined from concentration-response curves. Glucose-stimulated insulin secretion assays may be performed using pancreatic β-cell lines or primary islets.
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| Animal Protocol |
In vivo studies with Firuglipel have been conducted in rodent models of type 2 diabetes, including Sprague-Dawley rats and Zucker fatty rats. Doses ranging from 1-30 mg/kg are typically administered orally. Endpoints include glucose tolerance tests, insulin secretion measurements, GLP-1 levels, and glycohemoglobin concentrations. Efficacy is evaluated by improvements in glucose homeostasis and β-cell function preservation.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Firuglipel have been characterized in preclinical studies. The compound is orally available with good bioavailability. As a small molecule (MW 467.5) with favorable drug-like properties, it is suitable for oral administration. Detailed PK parameters such as half-life, Cmax, and AUC have been reported in the literature. The compound has advanced to clinical trials, indicating favorable PK profiles.
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| Toxicity/Toxicokinetics |
Firuglipel has been evaluated in clinical trials for type 2 diabetes mellitus. NCT02647320 is a 12-week study of DS-8500a in subjects with type 2 diabetes on metformin. The compound has progressed to Phase 2 clinical development. Toxicity data from preclinical safety studies would have been generated to support clinical advancement, though specific details are not provided in the available sources.
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| References | |
| Additional Infomation |
Firuglipel is also referred to as DS-8500, DS8500a, or DS-8500a. The IUPAC name is 4-[5-[(1R)-1-[4-(cyclopropanecarbonyl)phenoxy]propyl]-1,2,4-oxadiazol-3-yl]-2-fluoro-N-[(2R)-1-hydroxypropan-2-yl]benzamide. It is soluble in DMSO. The compound is for research use only and not for therapeutic or veterinary use.
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| Molecular Formula |
C25H26FN3O5
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|---|---|
| Molecular Weight |
467.489449977875
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| Exact Mass |
467.185
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| CAS # |
1371591-51-3
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| PubChem CID |
56959560
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.592
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| LogP |
3.51
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
34
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| Complexity |
700
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC[C@H](C1=NC(=NO1)C2=CC(=C(C=C2)C(=O)N[C@H](C)CO)F)OC3=CC=C(C=C3)C(=O)C4CC4
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| InChi Key |
LRXRIKVDAVVQCP-SPLOXXLWSA-N
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| InChi Code |
InChI=1S/C25H26FN3O5/c1-3-21(33-18-9-6-16(7-10-18)22(31)15-4-5-15)25-28-23(29-34-25)17-8-11-19(20(26)12-17)24(32)27-14(2)13-30/h6-12,14-15,21,30H,3-5,13H2,1-2H3,(H,27,32)/t14-,21-/m1/s1
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| Chemical Name |
4-[5-[(1R)-1-[4-(cyclopropanecarbonyl)phenoxy]propyl]-1,2,4-oxadiazol-3-yl]-2-fluoro-N-[(2R)-1-hydroxypropan-2-yl]benzamide
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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) |
DMSO : ~100 mg/mL (~213.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.35 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 (5.35 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1391 mL | 10.6954 mL | 21.3908 mL | |
| 5 mM | 0.4278 mL | 2.1391 mL | 4.2782 mL | |
| 10 mM | 0.2139 mL | 1.0695 mL | 2.1391 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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