WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 532054
CAS#: 191034-25-0
Description: L-168,049 is a non-peptidyl human glucagon receptor antagonist.
MedKoo Cat#: 532054
Name: L-168049
CAS#: 191034-25-0
Chemical Formula: C24H20BrClN2O
Exact Mass: 466.0448
Molecular Weight: 467.791
Elemental Analysis: C, 61.62; H, 4.31; Br, 17.08; Cl, 7.58; N, 5.99; O, 3.42
Synonym: L-168,049; L 168,049; L168,049; L-168049; L 168049; L168049;
IUPAC/Chemical Name: 4-[3-(5-bromo-2-propoxyphenyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl]pyridine
InChi Key: HHBOWXZOLYQFNY-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H20BrClN2O/c1-2-13-29-23-8-5-18(25)14-20(23)21-15-22(16-3-6-19(26)7-4-16)28-24(21)17-9-11-27-12-10-17/h3-12,14-15,28H,2,13H2,1H3
SMILES Code: ClC1=CC=C(C2=CC(C3=CC(Br)=CC=C3OCCC)=C(C4=CC=NC=C4)N2)C=C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | L-168049 is a potent, selective, orally active and non-competitive glucagon receptor antagonist with IC50s of 3.7 nM, 63 nM, and 60 nM for human, murine, and canine glucagon receptors, respectively. |
| In vitro activity: | Glucagon receptor was expressed in THP-1 cells, and 1 nM glucagon decreased the ratio of interleukin-1β to interleukin-10 gene expression, which was significantly prevented by L-168049. Reference: Diab Vasc Dis Res. 2020 May-Jun;17(5):1479164120965183. https://pubmed.ncbi.nlm.nih.gov/33076703/ |
| In vivo activity: | Taste responsiveness to sucrose in mice was similarly reduced upon acute and local disruption of glucagon signaling by the GlucR antagonist L-168,049. Reference: FASEB J. 2010 Oct;24(10):3960-9. https://pubmed.ncbi.nlm.nih.gov/20547661/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 48.39 | 103.44 | |
| Ethanol | 46.78 | 100.0 |
The following data is based on the product molecular weight 467.791 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Osaka N, Kushima H, Mori Y, Saito T, Hiromura M, Terasaki M, Yashima H, Ohara M, Fukui T, Matsui T, Hirano T, Yamagishi SI. Anti-inflammatory and atheroprotective properties of glucagon. Diab Vasc Dis Res. 2020 May-Jun;17(5):1479164120965183. doi: 10.1177/1479164120965183. PMID: 33076703; PMCID: PMC7919216. 2. Khare P, Mangal P, Baboota RK, Jagtap S, Kumar V, Singh DP, Boparai RK, Sharma SS, Khardori R, Bhadada SK, Kondepudi KK, Chopra K, Bishnoi M. Involvement of Glucagon in Preventive Effect of Menthol Against High Fat Diet Induced Obesity in Mice. Front Pharmacol. 2018 Nov 16;9:1244. doi: 10.3389/fphar.2018.01244. PMID: 30505271; PMCID: PMC6250823. 3. Elson AE, Dotson CD, Egan JM, Munger SD. Glucagon signaling modulates sweet taste responsiveness. FASEB J. 2010 Oct;24(10):3960-9. doi: 10.1096/fj.10-158105. Epub 2010 Jun 14. PMID: 20547661; PMCID: PMC2996909. |
| In vitro protocol: | 1. Osaka N, Kushima H, Mori Y, Saito T, Hiromura M, Terasaki M, Yashima H, Ohara M, Fukui T, Matsui T, Hirano T, Yamagishi SI. Anti-inflammatory and atheroprotective properties of glucagon. Diab Vasc Dis Res. 2020 May-Jun;17(5):1479164120965183. doi: 10.1177/1479164120965183. PMID: 33076703; PMCID: PMC7919216. 2. Khare P, Mangal P, Baboota RK, Jagtap S, Kumar V, Singh DP, Boparai RK, Sharma SS, Khardori R, Bhadada SK, Kondepudi KK, Chopra K, Bishnoi M. Involvement of Glucagon in Preventive Effect of Menthol Against High Fat Diet Induced Obesity in Mice. Front Pharmacol. 2018 Nov 16;9:1244. doi: 10.3389/fphar.2018.01244. PMID: 30505271; PMCID: PMC6250823. |
| In vivo protocol: | 1. Elson AE, Dotson CD, Egan JM, Munger SD. Glucagon signaling modulates sweet taste responsiveness. FASEB J. 2010 Oct;24(10):3960-9. doi: 10.1096/fj.10-158105. Epub 2010 Jun 14. PMID: 20547661; PMCID: PMC2996909. |
1: Yu R, Chen CR, Liu X, Kodra JT. Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones. J Mol Endocrinol. 2012 Jul 25;49(2):69-78. doi: 10.1530/JME-12-0051. PubMed PMID: 22693263.
2: Elson AE, Dotson CD, Egan JM, Munger SD. Glucagon signaling modulates sweet taste responsiveness. FASEB J. 2010 Oct;24(10):3960-9. doi: 10.1096/fj.10-158105. PubMed PMID: 20547661; PubMed Central PMCID: PMC2996909.
3: Dallas-Yang Q, Qureshi SA, Xie D, Zhang BB, Jiang G. Detection of glucagon-dependent GTPgammaS binding in high-throughput format. Anal Biochem. 2002 Feb 1;301(1):156-9. PubMed PMID: 11811981.
4: Shiao LL, Cascieri MA, Trumbauer M, Chen H, Sullivan KA. Generation of mice expressing the human glucagon receptor with a direct replacement vector. Transgenic Res. 1999 Aug;8(4):295-302. PubMed PMID: 10621976.
5: de Laszlo SE, Hacker C, Li B, Kim D, MacCoss M, Mantlo N, Pivnichny JV, Colwell L, Koch GE, Cascieri MA, Hagmann WK. Potent, orally absorbed glucagon receptor antagonists. Bioorg Med Chem Lett. 1999 Mar 8;9(5):641-6. PubMed PMID: 10201821.
6: Cascieri MA, Koch GE, Ber E, Sadowski SJ, Louizides D, de Laszlo SE, Hacker C, Hagmann WK, MacCoss M, Chicchi GG, Vicario PP. Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor. J Biol Chem. 1999 Mar 26;274(13):8694-7. PubMed PMID: 10085108.
