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MedKoo Cat#: 329514 | Name: Tropifexor
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Tropifexor, also known as LJN452, is a farnesoid X receptor agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH). Potent in vivo activity was demonstrated in rodent PD models by measuring the induction of FXR target genes in various tissues. Tropifexor has advanced into phase 2 human clinical trials in patients with NASH and PBC.

Chemical Structure

Tropifexor
Tropifexor
CAS#1383816-29-2

Theoretical Analysis

MedKoo Cat#: 329514

Name: Tropifexor

CAS#: 1383816-29-2

Chemical Formula: C29H25F4N3O5S

Exact Mass: 603.1451

Molecular Weight: 603.59

Elemental Analysis: C, 57.71; H, 4.18; F, 12.59; N, 6.96; O, 13.25; S, 5.31

Price and Availability

Size Price Availability Quantity
1mg USD 90.00 Ready to ship
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 750.00 Ready to ship
100mg USD 1,250.00 Ready to ship
200mg USD 2,250.00 Ready to ship
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Related CAS #
No Data
Synonym
Tropifexor; LJN452; LJN-452; LJN 452;
IUPAC/Chemical Name
2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid
InChi Key
VYLOOGHLKSNNEK-PIIMJCKOSA-N
InChi Code
InChI=1S/C29H25F4N3O5S/c30-21-9-15(27(37)38)10-23-25(21)34-28(42-23)36-16-7-8-17(36)12-18(11-16)39-13-20-24(35-41-26(20)14-5-6-14)19-3-1-2-4-22(19)40-29(31,32)33/h1-4,9-10,14,16-18H,5-8,11-13H2,(H,37,38)/t16-,17+,18+
SMILES Code
O=C(C1=CC(F)=C2N=C(N3[C@@]4([H])C[C@H](OCC5=C(C6CC6)ON=C5C7=CC=CC=C7OC(F)(F)F)C[C@]3([H])CC4)SC2=C1)O
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
More Info
Biological target:
Tropifexor (LJN452) is a highly potent agonist of FXR with an EC50 of 0.2 nM
In vitro activity:
Tropifexor (compound 1) is a novel and highly potent agonist of FXR with an EC50 of 0.2 nM. Robust induction of both BSEP and SHP genes is observed in primary cells by Tropifexor in a concentration-dependent manner. BSEP induction above vehicle (DMSO) control is observed at concentrations as low as 1 nM, while strong induction of SHP (15-fold above vehicle) is observed at 10 nM and modest induction of SHP at 1 nM (3-fold). Reference: J Med Chem. 2017 Dec 28;60(24):9960-9973. https://doi.org/10.1021/acs.jmedchem.7b00907
In vivo activity:
Tropifexor (compound 1) demonstrates highly potent induction of SHP and FGF15 in the ileum as doses as low as 0.1 mg/kg. In the liver, robust induction of SHP is observed at 0.01 mg/kg of Tropifexor with maximal levels of gene induction achieved at 0.3 mg/kg. Expression of CYP8B1 mRNA following 14 day treatment with Tropifexor is already apparent at the lowest dose (0.003 mg/kg), and CYP8B1 gene expression is fully repressed at doses above 0.03 mg/kg. Treatment of rats with Tropifexor exhibits a clear dose-dependent increase in plasma FGF15 protein, with maximal levels of FGF15 detected at 7 h postdose. Treatment with Tropifexor for 14 days produces a robust dose-dependent reduction in serum triglycerides and reaches a maximal response with a 0.3 mg/kg dose, resulting in a decrease of triglyceride levels to approximately 79% below the vehicle control group Reference: J Med Chem. 2017 Dec 28;60(24):9960-9973. https://doi.org/10.1021/acs.jmedchem.7b00907
Solvent mg/mL mM
Solubility
DMSO 80.7 133.64
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 603.59 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.

Recalculate based on batch purity %
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:
In vitro protocol:
1. Tully DC, Rucker PV, Chianelli D, Williams J, Vidal A, Alper PB, Mutnick D, Bursulaya B, Schmeits J, Wu X, Bao D, Zoll J, Kim Y, Groessl T, McNamara P, Seidel HM, Molteni V, Liu B, Phimister A, Joseph SB, Laffitte B. Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH). J Med Chem. 2017 Dec 28;60(24):9960-9973. doi: 10.1021/acs.jmedchem.7b00907. Epub 2017 Dec 8. PMID: 29148806.
In vivo protocol:
1. Tully DC, Rucker PV, Chianelli D, Williams J, Vidal A, Alper PB, Mutnick D, Bursulaya B, Schmeits J, Wu X, Bao D, Zoll J, Kim Y, Groessl T, McNamara P, Seidel HM, Molteni V, Liu B, Phimister A, Joseph SB, Laffitte B. Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH). J Med Chem. 2017 Dec 28;60(24):9960-9973. doi: 10.1021/acs.jmedchem.7b00907. Epub 2017 Dec 8. PMID: 29148806.
1: Anstee QM, Lucas KJ, Francque S, Abdelmalek MF, Sanyal AJ, Ratziu V, Gadano AC, Rinella M, Charlton M, Loomba R, Mena E, Schattenberg JM, Noureddin M, Lazas D, Goh GBB, Sarin SK, Yilmaz Y, Martic M, Stringer R, Kochuparampil J, Chen L, Rodriguez-Araujo G, Chng E, Naoumov NV, Brass C, Pedrosa MC. Tropifexor plus cenicriviroc combination versus monotherapy in nonalcoholic steatohepatitis: Results from the phase 2b TANDEM study. Hepatology. 2023 Oct 1;78(4):1223-1239. doi: 10.1097/HEP.0000000000000439. Epub 2023 May 11. PMID: 37162151; PMCID: PMC10521801. 2: Sanyal AJ, Lopez P, Lawitz EJ, Lucas KJ, Loeffler J, Kim W, Goh GBB, Huang JF, Serra C, Andreone P, Chen YC, Hsia SH, Ratziu V, Aizenberg D, Tobita H, Sheikh AM, Vierling JM, Kim YJ, Hyogo H, Tai D, Goodman Z, Schaefer F, Carbarns IRI, Lamle S, Martic M, Naoumov NV, Brass CA. Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial. Nat Med. 2023 Feb;29(2):392-400. doi: 10.1038/s41591-022-02200-8. Epub 2023 Feb 16. PMID: 36797481; PMCID: PMC9941046. 3: Yoneda M, Kobayashi T, Wada N, Otani T, Nogami A, Iwaki M, Nakajima A. Tropifexor, a selective non-acid farnesoid X receptor agonist, improved nonalcoholic steatohepatitis in a phase 2 trial, but several issues remain to be resolved. Hepatobiliary Surg Nutr. 2023 Oct 1;12(5):759-762. doi: 10.21037/hbsn-23-342. Epub 2023 Sep 4. PMID: 37886193; PMCID: PMC10598311. 4: Su YD, Wei XY, Su XH, Woshur G, Geng XN, Qiu XJ. Determination of Tropifexor in Beagle Dog Plasma by UPLC-MS/MS and Its Application in Pharmacokinetics. J Anal Methods Chem. 2022 Sep 17;2022:2823214. doi: 10.1155/2022/2823214. PMID: 36164482; PMCID: PMC9509244. 5: Jiang L, Xiao D, Li Y, Dai S, Qu L, Chen X, Guo M, Wei H, Chen Y. Structural basis of tropifexor as a potent and selective agonist of farnesoid X receptor. Biochem Biophys Res Commun. 2021 Jan 1;534:1047-1052. doi: 10.1016/j.bbrc.2020.10.039. Epub 2020 Oct 26. PMID: 33121679. 6: Ma C, Hu Y, Wang Y, Choza J, Wang J. Drug-Repurposing Screening Identified Tropifexor as a SARS-CoV-2 Papain-like Protease Inhibitor. ACS Infect Dis. 2022 May 13;8(5):1022-1030. doi: 10.1021/acsinfecdis.1c00629. Epub 2022 Apr 11. PMID: 35404564; PMCID: PMC9017246. 7: Liu Y, Xiao Y, Chen S, Tian X, Wang W, Wang Y, Cai W. The Farnesoid X Receptor Agonist Tropifexor Prevents Liver Damage in Parenteral Nutrition-fed Neonatal Piglets. J Pediatr Gastroenterol Nutr. 2021 Jul 1;73(1):e11-e19. doi: 10.1097/MPG.0000000000003135. PMID: 33783400. 8: Xiao Y, Wang W, Peng S, Lu Y, Du J, Cai W. Farnesoid X receptor agonist tropifexor detoxifies ammonia by regulating the glutamine metabolism and urea cycles in cholestatic livers. Eur J Pharmacol. 2024 Mar 5;966:176334. doi: 10.1016/j.ejphar.2024.176334. Epub 2024 Jan 28. PMID: 38286357. 9: Chen J, Stringer R, Shah B, Gu J, Zhang Y, Hackling M, Prince W, Woessner R. Drug-Drug Interaction Studies to Evaluate the Effect of Inhibition of UGT1A1 and CYP3A4 and Induction of CYP3A4 on the Pharmacokinetics of Tropifexor in Healthy Subjects. Clin Pharmacol Drug Dev. 2022 Nov;11(11):1253-1263. doi: 10.1002/cpdd.1140. Epub 2022 Aug 12. PMID: 35962468. 10: Schramm C, Wedemeyer H, Mason A, Hirschfield GM, Levy C, Kowdley KV, Milkiewicz P, Janczewska E, Malova ES, Sanni J, Koo P, Chen J, Choudhury S, Klickstein LB, Badman MK, Jones D. Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis. JHEP Rep. 2022 Jul 21;4(11):100544. doi: 10.1016/j.jhepr.2022.100544. PMID: 36267872; PMCID: PMC9576902.