GSK2330672 is a highly potent, nonabsorbable ASBT (apical sodium-dependent bile acid transporter) inhibitor (hASBT IC50=42 ± 3 nM) which 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.
Linerixibat 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Caco2-luc cells
20 µM
1 hour
To test the BSH-specific deconjugation ability of BAL probes in Caco2-luc cells, results showed that all BAL probes produced dose-dependent bioluminescent signals.
Sci Adv. 2021 Feb 3;7(6):eaaz9857.
4T1-luc cells
10 µM
1 hour
To test the BSH-specific deconjugation ability of BAL probes in 4T1-luc cells, results showed that all BAL probes produced dose-dependent bioluminescent signals.
Sci Adv. 2021 Feb 3;7(6):eaaz9857.
Linerixibat 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
FVB + luc transgenic mice
Oral
10 mg/kg
Single dose
To test the effect of Linerixibat on the deconjugation of the DCL probe, results showed no significant difference in bioluminescent signal before and after treatment, indicating that the deconjugation of BAL probes is primarily driven by microbial BSH activity.
Sci Adv. 2021 Feb 3;7(6):eaaz9857.
Mice
Cholestasis model
Oral gavage
10 mg/kg
Once daily for 3 weeks
To evaluate the therapeutic effect of Linerixibat in a cholestasis model, results showed that combination therapy of Linerixibat with OCA, cilofexor, or aldafermin effectively reduced faecal bile salt excretion and improved liver injury markers compared to ASBTi monotherapy.
JHEP Rep. 2023 Sep 25;6(1):100917
Mice
NPC1L1-EGFP knock-in mice
Oral
0.2 mg/mL
Once daily for 3 days
To evaluate the effect of Linerixibat on cholesterol absorption. The results showed that Linerixibat treatment increased bile acid excretion, reduced total cholesterol in serum, and increased cholesterol excretion in feces.
Nat Commun. 2023 Oct 13;14(1):6469
Mice
Transgenic luciferase reporter mice
Oral
10 mg/kg
Single dose
To evaluate the inhibitory effect of Linerixibat on ileal bile acid transporters (IBAT), the results showed no significant difference in bioluminescent signal from the DCL probe before and after Linerixibat treatment, indicating no significant contribution of host enzymes to probe unconjugation.
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