Tropifexor
Star0
This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Identification
- Generic Name
- Tropifexor
- DrugBank Accession Number
- DB16343
- Background
Tropifexor is under investigation in clinical trial NCT02516605 (A Multi-part, Double Blind Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in PBC Patients).
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 603.59
Monoisotopic: 603.145104743 - Chemical Formula
- C29H25F4N3O5S
- Synonyms
- Tropifexor
- External IDs
- LJN-452
- LJN452
- NVP-LJN452-NXA
Pharmacology
- Indication
Not Available
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Not Available
- Mechanism of action
Target Actions Organism UBile acid receptor agonistbinderHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- NMZ08KM76Z
- CAS number
- 1383816-29-2
- InChI Key
- VYLOOGHLKSNNEK-PIIMJCKOSA-N
- InChI
- 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+
- IUPAC 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
- SMILES
- OC(=O)C1=CC(F)=C2N=C(SC2=C1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCC1=C(ON=C1C1=C(OC(F)(F)F)C=CC=C1)C1CC1
References
- General References
- Not Available
- External Links
- ChemSpider
- 59718652
- BindingDB
- 50527040
- ChEMBL
- CHEMBL4298169
- PDBe Ligand
- GWF
- Wikipedia
- Tropifexor
- PDB Entries
- 7d42
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Non Alcoholic Steatohepatitis (NASH) 1 2 Completed Treatment Primary Bile Acid Diarrhea 1 2 Completed Treatment Primary Biliary Cholangitis 1 2 Terminated Treatment Fatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD / Non Alcoholic Steatohepatitis (NASH) 1 2 Terminated Treatment Non Alcoholic Steatohepatitis (NASH) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0129 mg/mL ALOGPS logP 5.36 ALOGPS logP 7.37 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 3.58 Chemaxon pKa (Strongest Basic) 0.77 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 97.92 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 140.09 m3·mol-1 Chemaxon Polarizability 57.01 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
1. DetailsBile acid receptor
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- AgonistBinder
- General Function
- Zinc ion binding
- Specific Function
- Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxyla...
- Gene Name
- NR1H4
- Uniprot ID
- Q96RI1
- Uniprot Name
- Bile acid receptor
- Molecular Weight
- 55913.915 Da
References
- Badman MK, Chen J, Desai S, Vaidya S, Neelakantham S, Zhang J, Gan L, Danis K, Laffitte B, Klickstein LB: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non-Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers. Clin Pharmacol Drug Dev. 2020 Apr;9(3):395-410. doi: 10.1002/cpdd.762. Epub 2019 Dec 10. [Article]
- Chianelli D, Rucker PV, Roland J, Tully DC, Nelson J, Liu X, Bursulaya B, Hernandez ED, Wu J, Prashad M, Schlama T, Liu Y, Chu A, Schmeits J, Huang DJ, Hill R, Bao D, Zoll J, Kim Y, Groessl T, McNamara P, Liu B, Richmond W, Sancho-Martinez I, Phimister A, Seidel HM, Badman MK, Joseph SB, Laffitte B, Molteni V: Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2020 Apr 23;63(8):3868-3880. doi: 10.1021/acs.jmedchem.9b01621. Epub 2020 Feb 5. [Article]
- Wang-Lakshman L, Miao Z, Wang L, Gu H, Kagan M, Gu J, McNamara E, Walles M, Woessner R, Camenisch G, Einolf HJ, Chen J: Evaluation of the Absorption, Metabolism, and Excretion of a Single Oral 1-mg Dose of Tropifexor in Healthy Male Subjects and the Concentration Dependence of Tropifexor Metabolism. Drug Metab Dispos. 2021 Jul;49(7):548-562. doi: 10.1124/dmd.120.000349. Epub 2021 May 5. [Article]
- Luo G, Lin X, Li Z, Xiao M, Li X, Zhang D, Xiang H: Structure-guided modification of isoxazole-type FXR agonists: Identification of a potent and orally bioavailable FXR modulator. Eur J Med Chem. 2021 Jan 1;209:112910. doi: 10.1016/j.ejmech.2020.112910. Epub 2020 Oct 7. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Hernandez ED, Zheng L, Kim Y, Fang B, Liu B, Valdez RA, Dietrich WF, Rucker PV, Chianelli D, Schmeits J, Bao D, Zoll J, Dubois C, Federe GC, Chen L, Joseph SB, Klickstein LB, Walker J, Molteni V, McNamara P, Meeusen S, Tully DC, Badman MK, Xu J, Laffitte B: Tropifexor-Mediated Abrogation of Steatohepatitis and Fibrosis Is Associated With the Antioxidative Gene Expression Profile in Rodents. Hepatol Commun. 2019 May 17;3(8):1085-1097. doi: 10.1002/hep4.1368. eCollection 2019 Aug. [Article]
- Xiao Y, Wang Y, Liu Y, Wang W, Tian X, Chen S, Lu Y, Du J, Cai W: A nonbile acid farnesoid X receptor agonist tropifexor potently inhibits cholestatic liver injury and fibrosis by modulating the gut-liver axis. Liver Int. 2021 Sep;41(9):2117-2131. doi: 10.1111/liv.14906. Epub 2021 May 18. [Article]
- Camilleri M, Nord SL, Burton D, Oduyebo I, Zhang Y, Chen J, Im K, Bhad P, Badman MK, Sanders DS, Walters JRF: Randomised clinical trial: significant biochemical and colonic transit effects of the farnesoid X receptor agonist tropifexor in patients with primary bile acid diarrhoea. Aliment Pharmacol Ther. 2020 Sep;52(5):808-820. doi: 10.1111/apt.15967. Epub 2020 Jul 23. [Article]
- Fiorucci S, Biagioli M, Baldoni M, Ricci P, Sepe V, Zampella A, Distrutti E: The identification of farnesoid X receptor modulators as treatment options for nonalcoholic fatty liver disease. Expert Opin Drug Discov. 2021 Oct;16(10):1193-1208. doi: 10.1080/17460441.2021.1916465. Epub 2021 May 5. [Article]
Drug created at December 15, 2020 20:02 / Updated at October 07, 2021 12:09