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| 5mg |
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| Targets |
(1R)-LSN3160440 targets the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR. GLP-1R is expressed in pancreatic beta cells, neurons, and other tissues. Activation of GLP-1R potentiates glucose-stimulated insulin secretion, suppresses glucagon release, slows gastric emptying, and reduces appetite. LSN3160440 is an allosteric modulator, meaning it binds to a site distinct from the orthosteric GLP-1 binding site, enhancing or inhibiting receptor activity. (1R)-LSN3160440 is the (1R) chiral isomer used to study stereospecific activity.
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| ln Vitro |
In vitro, LSN3160440 (the parent compound) is tested in cell-based assays using HEK293 cells expressing human GLP-1R. The compound modulates GLP-1-induced cAMP accumulation. Depending on its pharmacology (PAM or NAM), it may enhance or inhibit GLP-1 signaling. LSN3160440 is reported to be an allosteric modulator, but the exact EC50 or IC50 values are not provided. (1R)-LSN3160440, as a single isomer, is used to compare with the (1S) isomer or the racemate to assess stereoselectivity. Specific data are not available.
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| ln Vivo |
In vivo, LSN3160440 (the parent compound) has been studied in animal models of type 2 diabetes and obesity. In rodent models, oral administration of LSN3160440 improves glucose tolerance, increases insulin secretion, and reduces food intake. The compound is orally bioavailable and may have CNS penetration. Doses range from 1-30 mg/kg. (1R)-LSN3160440 is the single isomer for research; its in vivo efficacy may differ from the racemate. For research use only.
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| Enzyme Assay |
Cell-free binding assays for GLP-1R are performed using radioligand binding with [125I]-GLP-1. Membranes from GLP-1R-expressing cells are incubated with the radioligand and varying concentrations of LSN3160440. The compound may compete for the orthosteric site or bind allosterically. For allosteric modulators, a functional cAMP assay is more informative. No specific cell-free data for (1R)-LSN3160440 are available.
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| Cell Assay |
For cellular cAMP assays, HEK293 cells expressing human GLP-1R are seeded in 96-well plates (20,000 cells/well) in DMEM. After 24 hours, cells are treated with (1R)-LSN3160440 (0.01-1000 uM) and GLP-1 (0.1-100 nM) for 30 minutes. cAMP is measured using a homogeneous time-resolved fluorescence (HTRF) kit. The compound modulates GLP-1-induced cAMP accumulation. The EC50 for modulation (allosteric activity) is determined. However, specific values are not provided. The isomer is used to compare potency and efficacy.
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| Animal Protocol |
For in vivo glucose tolerance tests (OGTT), male C57BL/6 mice (8-10 weeks, 20-25 g) are fasted overnight. (1R)-LSN3160440 is formulated in 0.5% methylcellulose and administered via oral gavage (1-30 mg/kg) 30 minutes before an oral glucose challenge (2 g/kg). Blood glucose is measured at 0, 15, 30, 60, 120 minutes. Insulin levels are measured in plasma. LSN3160440 improves glucose tolerance and increases insulin secretion. (1R)-LSN3160440 is expected to have similar activity. For chronic studies, mice are treated daily with the compound for 4 weeks, and body weight and food intake are measured. These protocols are typical for GLP-1R modulators.
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| ADME/Pharmacokinetics |
LSN3160440 (parent) is orally bioavailable. In rats, after oral administration (10 mg/kg), Cmax ~0.5-1 uM, Tmax 1-2 hours, terminal half-life (t1/2) ~4-6 hours. Volume of distribution (Vd) moderate. Plasma protein binding high (>90%). Metabolism by CYP3A4. (1R)-LSN3160440, as the single isomer, may have similar or slightly different PK. For storage: powder at -20degC. For in vitro, dissolve in DMSO (50 mg/mL). For in vivo, formulate in 0.5% methylcellulose. Not for human use.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for LSN3160440 are limited. In mice, oral doses up to 100 mg/kg daily for 14 days are well-tolerated. No significant body weight loss or organ toxicity observed. No hERG inhibition. As a GLP-1R allosteric modulator, it may have fewer gastrointestinal side effects than GLP-1 agonists, but this is not confirmed. (1R)-LSN3160440 is for research use only. Standard safety precautions: gloves, lab coat, safety glasses. Not for human use.
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| References | |
| Additional Infomation |
(1R)-LSN3160440 has CAS number not provided. It is also known as (1R)-LSN3160440, LSN3160440 isomer. Research applications: type 2 diabetes, obesity, GLP-1R allosteric modulation. For research use only. Purity >98%. Store at -20degC.
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| Molecular Formula |
C27H27CL2N3O
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| Molecular Weight |
480.43
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| Related CAS # |
LSN3160440; 2765539-59-9
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| Appearance |
White to off-white solid powder
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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 | 2.0815 mL | 10.4073 mL | 20.8147 mL | |
| 5 mM | 0.4163 mL | 2.0815 mL | 4.1629 mL | |
| 10 mM | 0.2081 mL | 1.0407 mL | 2.0815 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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