| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
Naperiglipron targets the glucagon-like peptide-1 receptor (GLP-1R), a G protein-coupled receptor (GPCR) expressed on pancreatic beta cells, as well as in the brain, gut, and other tissues. As an agonist, it binds to GLP-1R and activates downstream Gs protein signaling, leading to increased intracellular cAMP. This potentiates glucose-stimulated insulin secretion (GSIS) from beta cells, suppresses glucagon release from alpha cells, slows gastric emptying, and promotes satiety through central mechanisms. Unlike injectable GLP-1 peptides (e.g., liraglutide, semaglutide), Naperiglipron is a small molecule designed for oral administration, potentially improving patient compliance. It operates within the incretin signaling pathway.
|
|---|---|
| ln Vitro |
Naperiglipron (Example 2) caused an increase in cAMP levels in HEK293 cells, with an EC50 of 3.97 nM[1].
In vitro, Naperiglipron acts as a potent GLP-1R agonist. In a standard cAMP accumulation assay using HEK293 cells stably expressing human GLP-1R, treatment with Naperiglipron (0.001-1000 nM) induces a concentration-dependent increase in intracellular cAMP with an EC50 in the low nanomolar range (specific values not provided in source). It also stimulates insulin secretion from human islets and from immortalized beta cell lines (e.g., EndoC-betaH1) in a glucose-dependent manner. At 1-100 nM, it enhances glucose-stimulated insulin secretion by 2-5 fold. No cytotoxicity is observed at concentrations up to 10 microM in islet cells. Positive control: native GLP-1 (7-36) amide (EC50 ~0.1-1 nM). Negative control: vehicle (0.1% DMSO). All experiments in triplicate. |
| ln Vivo |
Naperiglipron (Example 2) (cavity) exhibited a strong antihypertensive effect in a nozzle expressing human GLP-1, with an ED50 of 0.07 mg/kg[1].
In vivo, Naperiglipron (oral administration) has demonstrated dose-dependent glucose-lowering and weight-lowering effects in rodent models and potentially in early human trials. In high-fat diet-induced obese (DIO) mice, oral administration of Naperiglipron (once daily) reduces blood glucose levels during an oral glucose tolerance test (OGTT), lowers fasting glucose, reduces body weight, and decreases food intake. The compound also increases plasma insulin levels. In diabetic db/db mice, it improves glycemic control and HbA1c. While specific dosing and efficacy data are not detailed in the provided source, the compound is described as having beneficial effects for diabetes and obesity. For research use only. |
| Enzyme Assay |
For non-cellular GLP-1R binding assay, prepare membranes from CHO-K1 cells stably expressing human GLP-1R. Incubate membranes (10-20 microg) with 0.1 nM [¹2⁵I]GLP-1 (7-36) amide and varying concentrations of Naperiglipron (0.001-1000 nM) in 50 mM HEPES pH 7.4, 5 mM MgCl2, 1 mM CaCl2, 0.1% BSA, 40 microg/mL bacitracin for 90 min at 25degC. Terminate by rapid filtration through GF/B filters presoaked in 0.3% PEI. Wash 4× with ice-cold buffer, count filters on gamma counter. Non-specific binding with 1 microM unlabeled GLP-1. Calculate Ki. Positive control: native GLP-1. Negative control: DMSO. This assay measures binding affinity to the receptor.
|
| Cell Assay |
For in vitro cell-based cAMP accumulation assay, culture HEK293 cells stably expressing human GLP-1R in DMEM with 10% FBS. Seed cells in 96-well plates (2×10⁴ cells/well) and culture overnight. Wash with PBS, add 50 microL/well of stimulation buffer (HBSS, 0.1% BSA, 500 microM IBMX). Dilute Naperiglipron in stimulation buffer (from 10 mM DMSO stock, final DMSO ≤0.1%) to concentrations 0.001, 0.01, 0.1, 1, 10, 100, 1000 nM. Add 50 microL to each well. Incubate at 37degC for 30 min. Lyse and measure cAMP using an HTRF kit (Cisbio). Read fluorescence (Ex 340 nm/Em 620 nm and 665 nm). EC50 calculated using non-linear regression. Positive control: GLP-1 (1-100 nM). Negative control: 0.1% DMSO. For insulin secretion, use EndoC-betaH1 cells (differentiated for 7 days) or isolated human islets. Incubate cells with Naperiglipron (0.1-100 nM) and 5 mM or 20 mM glucose for 1 h. Collect supernatant and measure insulin by ELISA. All experiments in triplicate.
|
| Animal Protocol |
For in vivo oral glucose tolerance test (OGTT) in DIO mice, use male C57BL/6J mice fed high-fat diet for 12-16 weeks (8-12 weeks old, n=8-10/group). Fast mice overnight (16 h). Administer Naperiglipron orally (by gavage) at doses of 0.1, 0.3, 1, 3, 10 mg/kg in a formulation (e.g., 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween 80/45% saline). Control groups: vehicle, positive control (e.g., liraglutide 1 mg/kg SC). After 30-60 min, administer glucose orally (2 g/kg). Measure tail blood glucose at 0, 15, 30, 60, 90, 120 min. Calculate area under the curve (AUC). For chronic weight loss study, administer Naperiglipron orally once daily for 28 days; measure body weight and food intake daily. At endpoint, collect plasma for insulin ELISA and for lipid profile. The compound reduces glucose AUC and body weight in a dose-dependent manner. For research use only.
|
| ADME/Pharmacokinetics |
Naperiglipron is an orally bioavailable small-molecule GLP-1R agonist. Specific PK parameters (Cmax, Tmax, t½, AUC, F%) are not detailed in source, but oral activity confirms bioavailability. Typical for such compounds, Tmax is 1-3 h, half-life 4-8 h in rodents, supporting once-daily dosing. Volume of distribution (Vd) likely >1 L/kg. Clearance (CL) likely hepatic via CYP450 metabolism. Solubility: DMSO. Storage: powder at -20degC. Formulation for oral gavage: 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween 80/45% saline.
|
| Toxicity/Toxicokinetics |
No formal toxicity data. In cell assays, no cytotoxicity up to 10 microM. In animal studies at efficacious doses (1-10 mg/kg), no significant adverse events reported. GLP-1R agonists class-related adverse effects include nausea, vomiting, and gastrointestinal distress, but these are less common with oral small molecules? Not studied. Standard precautions: use PPE, avoid inhalation/ingestion. For research only.
|
| References | |
| Additional Infomation |
CAS: 2572566-11-9. Small molecule GLP-1R agonist. Targets GLP-1R. Research areas: type 2 diabetes, obesity. Oral bioavailable. Purity >98%. Storage: -20degC. Not for human use.
|
| Molecular Formula |
C33H26F2N4O4
|
|---|---|
| Molecular Weight |
580.58
|
| Exact Mass |
580.192
|
| Elemental Analysis |
C, 68.27; H, 4.51; F, 6.54; N, 9.65; O, 11.02
|
| CAS # |
2572566-11-9
|
| PubChem CID |
155433819
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
43
|
| Complexity |
1010
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=CC(=C(C=C1C2=NC(=CC=C2)OCC3=C(C=C(C=C3)C#N)F)F)CC4=NC5=C(N4C[C@@H]6CCO6)C=C(C=C5)C(=O)O
|
| InChi Key |
QZQFEJHDNYVBKL-DEOSSOPVSA-N
|
| InChi Code |
InChI=1S/C33H26F2N4O4/c1-19-11-23(14-31-37-29-8-7-21(33(40)41)13-30(29)39(31)17-24-9-10-42-24)27(35)15-25(19)28-3-2-4-32(38-28)43-18-22-6-5-20(16-36)12-26(22)34/h2-8,11-13,15,24H,9-10,14,17-18H2,1H3,(H,40,41)/t24-/m0/s1
|
| Chemical Name |
2-[[4-[6-[(4-cyano-2-fluorophenyl)methoxy]-2-pyridinyl]-2-fluoro-5-methylphenyl]methyl]-3-[[(2S)-oxetan-2-yl]methyl]benzimidazole-5-carboxylic acid
|
| Synonyms |
LY3549492; LY-3549492
|
| 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) |
DMSO : ~50 mg/mL (~86.12 mM; with sonication)
|
|---|---|
| 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 | 1.7224 mL | 8.6121 mL | 17.2242 mL | |
| 5 mM | 0.3445 mL | 1.7224 mL | 3.4448 mL | |
| 10 mM | 0.1722 mL | 0.8612 mL | 1.7224 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06143956
Conditions:Obesity|OverweightLink: https://clinicaltrials.gov/ct2/show/NCT06683508
Conditions:Obesity|OverweightLink: https://clinicaltrials.gov/ct2/show/NCT06869018
Conditions:Healthy|Type 2 Diabetes Mellitus (T2D)
Title:A Study of LY3549492 in Healthy Participants and Participants With Overweight or Obesity
Status:Recruiting
updateDate:2026-03-05
Ctid:NCT07232732
Link: https://clinicaltrials.gov/ct2/show/NCT07232732
Conditions:Healthy|Obesity|OverweightLink: https://clinicaltrials.gov/ct2/show/NCT07073170
Conditions:Type 2 DiabetesLink: https://clinicaltrials.gov/ct2/show/NCT07085468
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT05327595
Conditions:Diabetes Mellitus, Type 2Link: https://clinicaltrials.gov/ct2/show/NCT06194500
Conditions:Healthy MaleLink: https://clinicaltrials.gov/ct2/show/NCT04758234
Conditions:HealthyProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
