On the Pharmacology of Farnesoid X Receptor Agonists: Give me an "A", Like in "Acid"
Open accessAbstract
The Farnesoid X Receptor (FXR) has recently moved into the spotlight through the release of clinical data using Obeticholic Acid, an FXR agonist, that demonstrated effectiveness of this bile acid-like drug in patients with Primary Biliary Cirrhosis and Non-alcoholic Steatohepatitis (NASH). FXR holds the promise to become an attractive drug target for various conditions, from Non-alcoholic Fatty Liver Disease (NAFLD), NASH, liver cirrhosis, portal hypertension and a variety of cholestatic disorders to intestinal diseases including inflammatory bowel disease and bile acid diarrhea. Despite the wide therapeutic potential, surprisingly little is known about the pharmacology, pharmacokinetics and tissue distribution properties of drugs targeting FXR. Are tissue specific FXR agonists preferable for different indications, or might one type of ligand fit all purposes? This review aims to summarize the sparse data which are available on this clinically and pharmacologically relevant topic and provides a mechanistic model for understanding tissue-specific effects in vivo.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several FXR agonists are currently in clinical development.
“Currently, several FXR agonists are in clinical development52.”
From Unexplored therapeutic opportunities in the human genome (2018) · cites this paper as [52]
Cites
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
Inagaki, T., Moschetta, A., Lee, Y.-K., Peng, L., Zhao, G., Downes, M., Yu, R. T., Shelton, J. M., Richardson, J. A., Repa, J. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509592103 · Cited by 1,164 · see citing works
Gadaleta, R. M., van Erpecum, K. J., Oldenburg, B., Willemsen, E. C. L., Renooij, W., Murzilli, S., Klomp, L. W. J., Siersema, P. D., Schipper, M. E. I., Danese, S., et al. (2011) · Gut · doi:10.1136/gut.2010.212159 · Cited by 870 · see citing works
Pellicciari, R., Fiorucci, S., Camaioni, E., Clerici, C., Costantino, G., Maloney, P. R., Morelli, A., Parks, D. J., & Willson, T. M. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm025529g · Cited by 743 · see citing works
The bile acid receptor FXR is a modulator of intestinal innate immunity
Vavassori, P., Mencarelli, A., Renga, B., Distrutti, E., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803978 · Cited by 655 · see citing works
Farnesoid X receptor antagonizes nuclear factor κB in hepatic inflammatory response
Wang, Y.-D., Chen, W.-D., Wang, M., Yu, D., Forman, B. M., & Huang, W. (2008) · Hepatology · doi:10.1002/hep.22519 · Cited by 639 · see citing works
Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction
Jiang, C., Xie, C., Lv, Y., Li, J., Krausz, K. W., Shi, J., Brocker, C. N., Desai, D., Amin, S. G., Bisson, W. H., et al. (2015) · Nature Communications · doi:10.1038/ncomms10166 · Cited by 559 · see citing works
Beuers, U., Hohenester, S., de Buy Wenniger, L. J. M., Kremer, A. E., Jansen, P. L. M., & Elferink, R. P. J. O. (2010) · Hepatology · doi:10.1002/hep.23810 · Cited by 351 · see citing works
Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice
Zhang, L., Wang, Y.-D., Chen, W.-D., Wang, X., Lou, G., Liu, N., Lin, M., Forman, B. M., & Huang, W. (2012) · Hepatology · doi:10.1002/hep.25905 · Cited by 151 · see citing works
Chen, W.-D., Wang, Y.-D., Zhang, L., Shiah, S., Wang, M., Yang, F., Yu, D., Forman, B. M., & Huang, W. (2010) · Hepatology · doi:10.1002/hep.23390 · Cited by 115 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Unexplored therapeutic opportunities in the human genome
Oprea, T. I., Bologa, C. G., Brunak, S., Campbell, A., Gan, G. N., Gaulton, A., Gomez, S. M., Guha, R., Hersey, A., Holmes, J., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.14 · Cited by 378 · see citing works
- Authors
- Hambruch, E., Kinzel, O., & Kremoser, C.
- Affiliations
- Phenex Pharmaceuticals (Germany) (DE)
- ORCID
- Kinzel, Olaf
- Venue
- Nuclear Receptor Research
- Publisher
- KenzPub
- Published
- 2016
- Volume
- 3
- ISSN
- 2314-5706 (ISSN-L)
- 2314-5714
- OpenAlex
- W2412589310
- Cited by
- 3
- References
- 9
- Citations by year
- 2021: 2 · 2018: 1
- FWCI
- 0.18
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Nuclear Receptor Research (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- farnesoid X receptor, FXR agonists, obeticholic acid, pharmacokinetics, tissue distribution, primary biliary cirrhosis, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, cholestatic liver disease, bile acid diarrhea, inflammatory bowel disease, portal hypertension
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
