| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
GLP-1 receptor (GLP-1R). LSN3318839 is a potent, orally bioavailable positive allosteric modulator (PAM) of the GLP-1R. It has an EC50 of 14 nM. By binding to an allosteric site on the receptor, it stabilizes the interaction between the peptide ligand and GLP-1R, potentiating GLP-1 signaling.
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| ln Vitro |
LSN3318839 is a potent GLP-1R PAM with an EC50 of 14 nM. It potentiates increases in cAMP accumulation induced by the GLP-1R full agonist GLP-1 (9-36), but not the partial agonist GLP-1 (7-36), in INS-1 832/3 cells. This demonstrates its ability to selectively enhance full agonist-mediated signaling.
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| ln Vivo |
In vivo, LSN3318839 holds therapeutic potential for treating substance use disorders, anxiety-related conditions, and other central nervous system diseases where dysregulated signaling contributes to pathological behaviors. Its oral bioavailability makes it suitable for chronic administration. Its effects in vivo would be assessed in animal models of these disorders.
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| Enzyme Assay |
In vitro binding and functional assays are used to characterize LSN3318839 as a GLP-1R PAM. Radioligand binding assays or functional assays measuring cAMP accumulation are performed using GLP-1R-expressing cells in the presence of GLP-1 agonists to determine its EC50 of 14 nM and confirm its PAM activity.
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| Cell Assay |
Cellular assays for LSN3318839 involve treating GLP-1R-expressing cells (e.g., INS-1 832/3 cells) with the compound in the presence of GLP-1 agonists and measuring cAMP accumulation. The compound potentiates cAMP increases induced by full GLP-1R agonists but not partial agonists, confirming its PAM activity.
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| Animal Protocol |
In vivo efficacy of LSN3318839 would be evaluated in animal models of substance use disorders, anxiety, and other CNS diseases. The compound would be administered orally, and its effects on behavior, neurotransmitter signaling, and disease progression would be assessed. Its potential for treating CNS disorders is an area of active investigation.
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| ADME/Pharmacokinetics |
LSN3318839 is a small molecule with oral bioavailability. As a GLP-1R PAM, its pharmacokinetic properties support oral dosing. The compound should be stored under recommended conditions. It is for research use only and not intended for human therapeutic use.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for LSN3318839. As a GLP-1R PAM, its safety profile would be an important consideration. Potential toxicities could be related to its effects on GLP-1 signaling in various tissues. Standard preclinical safety studies would be required to evaluate its safety for potential therapeutic applications.
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| References |
[1]. Willard FS, et al. Discovery of an Orally Efficacious Positive Allosteric Modulator of the Glucagon-like Peptide-1 Receptor. J Med Chem. 2021 Mar 25;64(6):3439-3448.
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| Additional Infomation |
LSN3318839 (CAS#: 2764704-18-7) is a potent, orally bioavailable positive allosteric modulator (PAM) of the GLP-1 receptor with an EC50 of 14 nM. It acts as a molecular glue to stabilize ligand-receptor interactions. It holds therapeutic potential for substance use disorders and CNS diseases. It is a research tool for studying GLP-1R function.
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| Molecular Formula |
C26H23CL2N3O2
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|---|---|
| Molecular Weight |
480.385724306107
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| Exact Mass |
479.116
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| CAS # |
2764704-18-7
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| PubChem CID |
162641136
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
707
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C(=C(C=CC=1C1CC1)Cl)[C@@H](C)N1C=NC2C=NC(C3C=CC=CC=3[C@H](C(=O)O)C)=CC1=2
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| InChi Key |
JPJWHCNGSBCZMI-HUUCEWRRSA-N
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| InChi Code |
InChI=1S/C26H23Cl2N3O2/c1-14(26(32)33)17-5-3-4-6-19(17)21-11-23-22(12-29-21)30-13-31(23)15(2)24-20(27)10-9-18(25(24)28)16-7-8-16/h3-6,9-16H,7-8H2,1-2H3,(H,32,33)/t14-,15-/m1/s1
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| Chemical Name |
(2R)-2-[2-[1-[(1R)-1-(2,6-dichloro-3-cyclopropylphenyl)ethyl]imidazo[4,5-c]pyridin-6-yl]phenyl]propanoic acid
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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: 10 mg/mL (20.82 mM)
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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 | 2.0816 mL | 10.4082 mL | 20.8164 mL | |
| 5 mM | 0.4163 mL | 2.0816 mL | 4.1633 mL | |
| 10 mM | 0.2082 mL | 1.0408 mL | 2.0816 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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