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 rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
UBile acid receptor
agonist
binder
Humans
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 outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
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
ChemSpider
59718652
BindingDB
50527040
ChEMBL
CHEMBL4298169
PDBe Ligand
GWF
Wikipedia
Tropifexor
PDB Entries
7d42

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentNon Alcoholic Steatohepatitis (NASH)1
2CompletedTreatmentPrimary Bile Acid Diarrhea1
2CompletedTreatmentPrimary Biliary Cholangitis1
2RecruitingTreatmentNon Alcoholic Steatohepatitis (NASH)1
2TerminatedTreatmentFatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD / Non Alcoholic Steatohepatitis (NASH)1
2TerminatedTreatmentNon Alcoholic Steatohepatitis (NASH)1
1CompletedTreatmentFatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD1
1CompletedTreatmentLiver Disease1

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
PropertyValueSource
Water Solubility0.0129 mg/mLALOGPS
logP5.36ALOGPS
logP7.37ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)3.58ChemAxon
pKa (Strongest Basic)0.77ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area97.92 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity140.09 m3·mol-1ChemAxon
Polarizability57.01 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Binder
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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