| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
PPARγ
AMG-131 targets peroxisome proliferator-activated receptor gamma (PPARγ). It acts as a selective PPARγ partial agonist. By activating PPARγ, AMG-131 improves insulin sensitivity and glycemic control. Unlike full PPARγ agonists (thiazolidinediones), partial agonists may have a more favorable safety profile with reduced side effects such as weight gain and fluid retention. |
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| ln Vitro |
AMG131 (INT131) exhibits a Ki of approximately 10 nM when binding to PPARγ, displacing Rosiglitazone. Its affinity is approximately 20 times greater than that of either Rosiglitazone or Pioglitazone, and it has a selectivity of more than 1000 times for PPARγ over PPARα, PPARδ, or a group of other nuclear receptors. With no binding to PPARα or δ at 10 μM, 1000 times over the Ki for PPARγ, AMG131 exhibits high selectivity for PPARγ[1].
In vitro, AMG-131 acts as a selective PPARγ partial agonist. It activates PPARγ-mediated gene expression in cell-based reporter assays. Its potency and efficacy as a PPARγ partial agonist have been demonstrated in these assays. These in vitro activities confirm its profile as a selective PPARγ modulator with hypoglycemic potential. |
| ln Vivo |
AMG131 (INT131; 80 mg/kg; 14-day oral treatment) improves glucose tolerance after in Zucker (fa/fa) rats following[2]
In vivo, AMG-131 is an orally administered therapy for type 2 diabetes. It is expected to lower blood glucose levels by improving the body's responsiveness to insulin. It has been investigated for use/treatment in diabetes mellitus type 2. However, specific details of in vivo efficacy studies are not extensively detailed in the available literature. |
| Enzyme Assay |
The in vitro receptor binding assay for AMG-131 typically involves radioligand displacement studies using PPARγ protein. The compound's affinity is determined by measuring its ability to displace a specific radiolabeled ligand from the receptor. Functional agonism is assessed using transactivation assays in cells expressing PPARγ. These assays provide a direct measure of the compound's binding and functional activity at PPARγ.
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| Cell Assay |
In vitro cellular assays for AMG-131 assess its functional activity at PPARγ. Cells expressing PPARγ are treated with the compound, and PPARγ-mediated gene expression is measured using reporter genes. These assays demonstrate the compound's ability to activate PPARγ in a relevant cellular context. The compound's effects on glucose metabolism can also be assessed in cellular models.
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| Animal Protocol |
Male Zucker fatty (fa/fa) rats ages 7-8 weeks[2]
80 mg/kg Administered once daily by oral gavage for 14 days In vivo animal studies for AMG-131 have been conducted in models of type 2 diabetes to assess its hypoglycemic effects. However, specific details of these studies are not extensively detailed in the available literature. The compound has been investigated in clinical trials for type 2 diabetes. |
| ADME/Pharmacokinetics |
AMG-131 is orally administered. It is absorbed from the gastrointestinal tract and distributed throughout the body. Its pharmacokinetic properties support its use as an oral therapeutic agent for type 2 diabetes. However, specific parameters such as half-life and bioavailability are not extensively detailed in the available literature.
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| Toxicity/Toxicokinetics |
Specific toxicity data for AMG-131 are not extensively detailed in the available literature. As a PPARγ partial agonist, its toxicity profile is likely related to its pharmacological activity. However, its partial agonist activity may result in a more favorable safety profile compared to full PPARγ agonists. Preclinical toxicology studies would be required to assess its safety margin.
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| References | |
| Additional Infomation |
AMG-131 (T131) is an oral medication that promises to lower blood glucose levels in patients with type 2 diabetes by improving the body's responsiveness to insulin. T131 is a selective modulator of peroxisome proliferator-activated receptor γ (PPARγ), a receptor involved in regulating the body's response to insulin. The structure of T131 is independent of thiazolidinedione PPARγ agonists, including Actos and Avandia.
Drug Indications Its research is underway for the treatment of type 2 diabetes.Mechanism of Action T131 is a selective modulator of peroxisome proliferator-activated receptor γ (PPARγ), a receptor involved in regulating the body's responsiveness to insulin. The structure of T131 is independent of thiazolidinedione PPARγ agonists, including Actos and Avandia. Pharmacodynamics T131 is an oral medication expected to lower blood glucose levels in patients with type 2 diabetes by improving the body's responsiveness to insulin. The structure of T131 is not related to thiazolidinedione PPARγ agonists (including Actos and Avandia). AMG-131 is a novel, potent, selective PPARγ partial agonist and hypoglycemic agent also known as INT-131. It is an orally administered therapy for type 2 diabetes that improves insulin sensitivity. It is a non-thiazolidinedione (non-TZD) selective PPARγ modulator. It is a research compound and is not approved for clinical use. |
| Molecular Formula |
C21H12CL4N2O3S
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|---|---|
| Molecular Weight |
514.20858001709
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| Exact Mass |
476
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| Elemental Analysis |
C, 49.05; H, 2.35; Cl, 27.58; N, 5.45; O, 9.33; S, 6.24
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| CAS # |
315224-26-1
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| Related CAS # |
849738-78-9 (besylate);315224-26-1;
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| PubChem CID |
10229498
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| Appearance |
White to light yellow solid powder
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| LogP |
6.699
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
697
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CC=C(S(NC2=CC(Cl)=C(OC3C=NC4=CC=CC=C4C=3)C(Cl)=C2)(=O)=O)C(Cl)=C1
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| InChi Key |
NMRWDFUZLLQSBN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H12Cl4N2O3S/c22-13-5-6-20(16(23)8-13)31(28,29)27-14-9-17(24)21(18(25)10-14)30-15-7-12-3-1-2-4-19(12)26-11-15/h1-11,27H
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| Chemical Name |
2,4-dichloro-N-(3,5-dichloro-4-quinolin-3-yloxyphenyl)benzenesulfonamide
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| Synonyms |
AMG-131; AMG131; AMG 131; INT-131; INT-131; NT-131; T-131; T-0903131; ibrigampar
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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: ~250 mg/mL (~486.2 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.05 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 20.8 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: ≥ 2.08 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9447 mL | 9.7237 mL | 19.4473 mL | |
| 5 mM | 0.3889 mL | 1.9447 mL | 3.8895 mL | |
| 10 mM | 0.1945 mL | 0.9724 mL | 1.9447 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02638038 | Completed | Drug: INT131 | Multiple Sclerosis, Relapsing Remitting | InteKrin Therapeutics, Inc. | February 2015 | Phase 2 |
| NCT00952445 | Completed | Drug: T0903131 Besylate Drug: Placebo |
Diabetes Mellitus, Type II | InteKrin Therapeutics, Inc. | December 2003 | Phase 2 |
| NCT00631007 | Completed | Drug: INT131 besylate Drug: Pioglitazone HCl |
Type 2 Diabetes Mellitus | InteKrin Therapeutics, Inc. | February 2008 | Phase 2 |
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