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Chemical Structure| 1345982-69-5 Chemical Structure| 1345982-69-5

Structure of Linerixibat
CAS No.: 1345982-69-5

Chemical Structure| 1345982-69-5

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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.

Synonyms: Gsk2330672

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Product Details of Linerixibat

CAS No. :1345982-69-5
Formula : C28H38N2O7S
M.W : 546.68
SMILES Code : 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
Synonyms :
Gsk2330672
MDL No. :N/A

Safety of Linerixibat

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Caco2-luc cells 20 µM 1 h 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. PMC7857686
4T1-luc cells 10 µM 1 h 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. PMC7857686

In Vivo:

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. PMC7857686
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. PMC10701132
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. PMC10575946
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. PMC7857686

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT05448170 Pruritus AVAILABLE - -
NCT05393076 Pruritus PHASE1 COMPLETED 2022-12-06 GSK Investigational Site, Orla... More >>ndo, Florida, 32809, United States|GSK Investigational Site, San Antonio, Texas, 78215, United States Less <<
NCT04167358 Cholestasis PHASE3 ACTIVE_NOT_RECRUITING 2027-08-31 GSK Investigational Site, Davi... More >>s, California, 95817, United States|GSK Investigational Site, West Hollywood, California, 90048, United States|GSK Investigational Site, Miami, Florida, 33136, United States|GSK Investigational Site, Detroit, Michigan, 48377, United States|GSK Investigational Site, New York, New York, 10016, United States|GSK Investigational Site, Durham, North Carolina, 27710, United States|GSK Investigational Site, Morrisville, North Carolina, 27560, United States|GSK Investigational Site, Philadelphia, Pennsylvania, 19104, United States|GSK Investigational Site, Dallas, Texas, 75390, United States|GSK Investigational Site, Houston, Texas, 77030, United States|GSK Investigational Site, Seattle, Washington, 98105, United States|GSK Investigational Site, Buenos Aires, C1061AAS, Argentina|GSK Investigational Site, Capital Federal, C1181ACI, Argentina|GSK Investigational Site, Ciudad AutOnoma de Buenos Aire, 1118, Argentina|GSK Investigational Site, Ciudad Autonoma De Bueno, C1056ABI, Argentina|GSK Investigational Site, Rosario, S2002KDT, Argentina|GSK Investigational Site, Santa Fe, 3000, Argentina|GSK Investigational Site, Botucatu, 18618686, Brazil|GSK Investigational Site, Brasilia, 70335-900, Brazil|GSK Investigational Site, Porto Alegre, 90035003, Brazil|GSK Investigational Site, Salvador, 40110-160, Brazil|GSK Investigational Site, Sofia, 1618, Bulgaria|GSK Investigational Site, Edmonton, Alberta, T6G 2X8, Canada|GSK Investigational Site, Toronto, Ontario, M5G 2C4, Canada|GSK Investigational Site, Beijing, 100032, China|GSK Investigational Site, Beijing, 100069, China|GSK Investigational Site, Changchun, 130021, China|GSK Investigational Site, Chongqing, 400042, China|GSK Investigational Site, Guangzhou, 510630, China|GSK Investigational Site, Nanchang, 330006, China|GSK Investigational Site, Nanjing, 210003, China|GSK Investigational Site, Shanghai, 200127, China|GSK Investigational Site, Tianjin, 300000, China|GSK Investigational Site, Plzen, 30100, Czechia|GSK Investigational Site, Praha 4, 140 21, Czechia|GSK Investigational Site, Lille, 59037, France|GSK Investigational Site, Erlangen, 91054, Germany|GSK Investigational Site, Muenster, 48149, Germany|GSK Investigational Site, Haifa, 34362, Israel|GSK Investigational Site, Holon, 58100, Israel|GSK Investigational Site, Jerusalem, 91120, Israel|GSK Investigational Site, Rehovot, 76100, Israel|GSK Investigational Site, Milano, 20142, Italy|GSK Investigational Site, Modena, 41126, Italy|GSK Investigational Site, Monza, 20900, Italy|GSK Investigational Site, Napoli, 80131, Italy|GSK Investigational Site, Negrar Verona, 37024, Italy|GSK Investigational Site, Padova, 35128, Italy|GSK Investigational Site, Palermo, 90127, Italy|GSK Investigational Site, Roma, 00168, Italy|GSK Investigational Site, Chiba, 270-1694, Japan|GSK Investigational Site, Ehime, 791-0295, Japan|GSK Investigational Site, Fukui, 918-8503, Japan|GSK Investigational Site, Gunma, 371-8511, Japan|GSK Investigational Site, Hiroshima, 730-8619, Japan|GSK Investigational Site, Hiroshima, 734-8551, Japan|GSK Investigational Site, Hokkaido, 006-8555, Japan|GSK Investigational Site, Kagawa, 760-8557, Japan|GSK Investigational Site, Kanagawa, 259-1143, Japan|GSK Investigational Site, Nagano, 390-8621, Japan|GSK Investigational Site, Nagasaki, 856-8562, Japan|GSK Investigational Site, Nara, 634-8522, Japan|GSK Investigational Site, Osaka, 545-8586, Japan|GSK Investigational Site, Osaka, 591-8025, Japan|GSK Investigational Site, Shizuoka, 431-3192, Japan|GSK Investigational Site, Tokyo, 113-8603, Japan|GSK Investigational Site, Tokyo, 162-8655, Japan|GSK Investigational Site, Tokyo, 173-8606, Japan|GSK Investigational Site, Tokyo, 181-8611, Japan|GSK Investigational Site, Ciudad de MExico, 06700, Mexico|GSK Investigational Site, Mexico City, 14080, Mexico|GSK Investigational Site, Monterrey, 64020, Mexico|GSK Investigational Site, Czestochowa, 42-217, Poland|GSK Investigational Site, Katowice, 40-659, Poland|GSK Investigational Site, Myslowice, 41-400, Poland|GSK Investigational Site, Warszawa, 03-712, Poland|GSK Investigational Site, Wroclaw, 51-162, Poland|GSK Investigational Site, Kemerovo, 650000, Russian Federation|GSK Investigational Site, Moscow, 119121, Russian Federation|GSK Investigational Site, Samara, 443063, Russian Federation|GSK Investigational Site, Barcelona, 08036, Spain|GSK Investigational Site, Madrid, 28007, Spain|GSK Investigational Site, Madrid, 28041, Spain|GSK Investigational Site, Sevilla, 41013, Spain|GSK Investigational Site, Valencia, 46026, Spain|GSK Investigational Site, Basingstoke, RG24 9NA, United Kingdom|GSK Investigational Site, Glasgow, G31 2ER, United Kingdom|GSK Investigational Site, Hull, HU3 2JZ, United Kingdom|GSK Investigational Site, London, NW3 2QG, United Kingdom|GSK Investigational Site, Newcastle Upon Tyne, NE4 5PL, United Kingdom|GSK Investigational Site, Nottingham, NG7 2UH, United Kingdom|GSK Investigational Site, Plymouth, PL6 8DH, United Kingdom|GSK Investigational Site, Reading Berkshire, RG1 5AN, United Kingdom|GSK Investigational Site, Southampton, SO16 6YD, United Kingdom|GSK Investigational Site, Surrey, RH1 5RH, United Kingdom Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.83mL

0.37mL

0.18mL

9.15mL

1.83mL

0.91mL

18.29mL

3.66mL

1.83mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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