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Purity: ≥98%
Linerixibat (formerly known as GSK2330672; GSK-2330672) is a novel, highly potent and nonabsorbable inhibitor of ASBT (apical sodium-dependent bile acid transporter) under development for cholestatic pruritus in primary biliary cholangitis. It inhibits ASBT with an IC50 of 42 ± 3 nM for hASBT. Linerixibat lowers glucose in an animal model of type 2 diabetes and shows excellent developability properties for evaluating the potential therapeutic utility of a nonabsorbable ASBT inhibitor for treatment of patients with type 2 diabetes. The apical sodium-dependent bile acid transporter (ASBT) transports bile salts from the lumen of the gastrointestinal (GI) tract to the liver via the portal vein.
ln Vitro |
Compound 56, also known as zwitterionic, non-hygroscopic crystalline salt form, has good solubility (>7 mg/mL) at pH 7.4, great thermal stability, and does not generate artifacts or reactivity [1].
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ln Vivo |
In animal models of type 2 diabetes, treatment with Linerixibat (GSK2330672; 0.05–10 mg/kg; side wall gavage; twice daily for 14 days; gravimetric ZDF content) lowers diabetes [1].
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Animal Protocol |
Animal/Disease Models: Male Zucker diabetic fat (ZDF) rat [1]
Doses: 0.05 mg/kg, 0.1 mg/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg twice (two times) daily; Results lasting 14 days: Glycated hemoglobin (HbA1c) diminished by 1.30-1.64%, non-fasting blood glucose diminished by more than 50% to less than 200 mg/dL, and plasma insulin increased Dramatically. |
References |
[1]. Wu Y, et al. Discovery of a highly potent, nonabsorbable apical sodium-dependent bile acid transporter inhibitor (GSK2330672) for treatment of type 2 diabetes. J Med Chem. 2013 Jun 27;56(12):5094-114.
[2]. Wang Y, et al. HNF4α Regulates CSAD to Couple Hepatic Taurine Production to Bile Acid Synthesis in Mice. Gene Expr. 2018 Aug 22;18(3):187-196. [3]. Linerixibat (GSK2330672) granted Orphan Status. September 24, 2019. |
Molecular Formula |
C28H38N2O7S
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Molecular Weight |
546.675527095795
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CAS # |
1345982-69-5
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SMILES |
O=C(O)CC(NCC1=C(OC)C=C(C2=C1)[C@@H](C3=CC=CC=C3)N[C@](CC)(CCCC)CS2(=O)=O)CC(O)=O
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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 : ~50 mg/mL (~91.46 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.57 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8292 mL | 9.1461 mL | 18.2922 mL | |
5 mM | 0.3658 mL | 1.8292 mL | 3.6584 mL | |
10 mM | 0.1829 mL | 0.9146 mL | 1.8292 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.