Target Profile Prediction: Cross‐Activation of Peroxisome Proliferator‐Activated Receptor (PPAR) and Farnesoid X Receptor (FXR)

Steri, Ramona; Schneider, Petra; Klenner, Alexander; Rupp, Matthias; Kriegl, Jan M.; Schubert‐Zsilavecz, Manfred; Schneider, Gisbert

doi:10.1002/minf.200900009

Cited by 8 publications

(3 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(E)-3-[1-(4-tert-Butylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl]acrylic acid ( 18 ) [75] , a compound derived from a FXR/PPAR agonist [76] , is a selective FXR agonist. 18 activates FXR with EC 50 = 1.4 μM, and Kd = 4 μM [75] .…”

Section: Ligand-binding Properties Of Fxrmentioning

confidence: 99%

Farnesoid X receptor (FXR): Structures and ligands

Jiang

Zhang

Xiao

et al. 2021

Computational and Structural Biotechnology Journal

122

View full text Add to dashboard Cite

show abstract

Section: Ligand-binding Properties Of Fxrmentioning

confidence: 99%

Farnesoid X receptor (FXR): Structures and ligands

Jiang

Zhang

Xiao

et al. 2021

Computational and Structural Biotechnology Journal

122

View full text Add to dashboard Cite

show abstract

“…Within the convex hulls spanned by a total of five oxadiazole clusters (Figure 1C), we found a prevalence of known ligands of peroxisome proliferator activated receptors (PPARs), 5‐lipoxygenase (5‐LO) and various G‐protein coupled receptors (GPCRs) (Figure S3). By analogy reasoning, partially similar biological activity can be expected 29–31. As none of the virtual oxadiazoles contained an acidic head group, which is an essential structural feature of most of the known PPAR agonists,32,33 we decided to investigate only for 5‐LO inhibition for the sake of this proof‐of‐concept study.…”

Section: Results Of Retrospective Virtual Screening Given As Average mentioning

confidence: 96%

From Virtual Screening to Bioactive Compounds by Visualizing and Clustering of Chemical Space

Klenner

Hähnke

Geppert

et al. 2011

Molecular Informatics

Self Cite

View full text Add to dashboard Cite

“…In 2010, Steri et al 16 discovered FXR ligand 5 in a virtual screening campaign. In vitro, 5 displayed FXR agonism with an EC 50 value of 13 μM and simultaneously activated the peroxisome proliferator-activated receptor α (PPARα) with EC 50 = 1.3 μM.…”

mentioning

confidence: 99%

A New FXR Ligand Chemotype with Agonist/Antagonist Switch

Helmstädter

Vietor

Sommer

et al. 2021

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

Therapeutic modulation of the bile acid-sensing transcription factor farnesoid X receptor (FXR) is an appealing strategy to counteract hepatic and metabolic diseases. Despite the availability of several highly potent FXR agonists structural diversity of FXR modulators is limited, and new ligand scaffolds are needed. Here we report structure–activity relationship elucidation of a new FXR modulator chemotype whose activity can be tuned between agonism and antagonism by two minor structural modifications. Starting from a weak FXR/PPAR agonist, we have developed selective FXR activators and antagonists with nanomolar to low-micromolar potencies and binding affinities. The new FXR ligand chemotype modulates the FXR activity in the native cellular setting, is endowed with favorable metabolic stability, and lacks cytotoxicity. It valuably expands the collection of FXR modulators as a new scaffold for FXR-targeted drug discovery.

show abstract

Target Profile Prediction: Cross‐Activation of Peroxisome Proliferator‐Activated Receptor (PPAR) and Farnesoid X Receptor (FXR)

Cited by 8 publications

References 61 publications

Farnesoid X receptor (FXR): Structures and ligands

Farnesoid X receptor (FXR): Structures and ligands

From Virtual Screening to Bioactive Compounds by Visualizing and Clustering of Chemical Space

A New FXR Ligand Chemotype with Agonist/Antagonist Switch

Contact Info

Product

Resources

About