Linerixibat

Catalog No.S3529 Batch:S352901

Technical Data

Formula	C₂₈H₃₈N₂O₇S
Molecular Weight	546.68	CAS No.	1345982-69-5
Solubility (25°C)*	In vitro	DMSO	50 mg/mL (91.46 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description	Linerixibat (GSK 2330672, GSK 672), a highly potent, nonabsorbable inhibitor of apical sodium dependent bile acid transporter (ABST), also known as the ileal bile acid transporter (IBAT), is used to the treatment of cholestatic pruritus in primary biliary Cholangitis. The IC50 of human ASBT is 42 nM.
In vitro	The zwitterionic, nonhygroscopic, crystalline salt form of Linerixibat shows good aqueous solubility at pH 7.4 (>7 mg/mL), excellent thermal stability, and does not generate reactive or humanspecific metabolite, characteristics.^[3]
In vivo	Linerixibat (twice daily; for 14 days) treatment lowers glucose in an animal model of type 2 diabetes.^[3]

Protocol (from reference)

Cell Assay:^{^[3]}	Cell lines Human Multi-Drug Resistance 1-Madin-Darby Canine Kidney (HMDR1-) cells Concentrations 3 μM Incubation Time 30 min Method HMDR1-MDCK cells are seeded at 6.6 × 105 cells/well onto 12-well polycarbonate Transwells filter membranes with 0.4 μm pore size. After three days, media is removed from both the apical and basolateral chambers and replaced with transport buffer (HBSS containing 25 mM glucose and 25 mM HEPES) containing the P-gp inhibitor GF120918A at a final concentration of 2 μM. After a 30 min equilibration, the transport buffer is removed from the apical chambers and replaced with fastedstate simulated intestinal fluid containing 3 μM Linerixibat, 2 μM GF120918A, 25 mM glucose, and 250 μM Lucifer Yellow CH. Next, the transport buffer is removed from the basolateral chambers and replaced with transport buffer containing 1% (w/v) human serum albumin and 2 μM GF120918A. After 60 min incubation at 37 °C, samples are collected from the apical (donor) and basolateral (receiver) compartments and added to acetonitrile (1:1 and 1:2 (v/v), respectively). Receiver samples are then centrifuged and the supernatants are removed and analyzed by LC-MS/MS.

Cell Assay:^{^[3]}

Cell lines
Human Multi-Drug Resistance 1-Madin-Darby Canine Kidney (HMDR1-) cells
Concentrations
3 μM
Incubation Time
30 min
Method
HMDR1-MDCK cells are seeded at 6.6 × 105 cells/well onto 12-well polycarbonate Transwells filter membranes with 0.4 μm pore size. After three days, media is removed from both the apical and basolateral chambers and replaced with transport buffer (HBSS containing 25 mM glucose and 25 mM HEPES) containing the P-gp inhibitor GF120918A at a final concentration of 2 μM. After a 30 min equilibration, the transport buffer is removed from the apical chambers and replaced with fastedstate simulated intestinal fluid containing 3 μM Linerixibat, 2 μM GF120918A, 25 mM glucose, and 250 μM Lucifer Yellow CH. Next, the transport buffer is removed from the basolateral chambers and replaced with transport buffer containing 1% (w/v) human serum albumin and 2 μM GF120918A. After 60 min incubation at 37 °C, samples are collected from the apical (donor) and basolateral (receiver) compartments and added to acetonitrile (1:1 and 1:2 (v/v), respectively). Receiver samples are then centrifuged and the supernatants are removed and analyzed by LC-MS/MS.

References

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.