Structure Basis of Bigelovin as a Selective RXR Agonist with a Distinct Binding Mode

Zhang, Haitao; Li, Li; Chen, Lili; Hu, Lihong; Jiang, Hualiang; Shen, Xu

doi:10.1016/j.jmb.2011.01.032

Cited by 35 publications

(34 citation statements)

References 42 publications

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“…Shen and coworkers reported the structure (3OZJ) of the dimeric bigelovin–RXRα LBD–SRC-1 CoA peptide complex [102] (Fig. 7).…”

Section: Dimerizationmentioning

confidence: 99%

“…The sesquiterpene bigelovin is another ingredient found in Chinese herbal medicine and is reported to induce leukemia cell growth arrest and apoptosis [103]. Bigelovin had an AC 50 value of 4.9 μM for activating the GAL4-RXRα LBD in a luciferase reporter assay in HEK293T cells and a K d value for binding the RXRα LBD of 8.7 μM [102]. It slightly enhanced activation of the GAL4-PPARγ LBD by rosiglitazone and GAL4-FXR LBD by chenodeoxycholic acid in this reporter assay but not that of the GAL4-LXRα LBD by TO-901317.…”

Section: Dimerizationmentioning

confidence: 99%

“…The acetyl group of bigelovin overlapped the carboxylate of rhein. Again, the major ligand interactions observed in the LBP were hydrophobic [102]. On the basis of its transactivation behavior, the question arises as to why the SRC-1 CoA peptide would bind the bigelovin–RXRα LBD complex.…”

Section: Dimerizationmentioning

confidence: 99%

“…In 3OZJ, H12 of each monomer formed an AF-2 surface with its H3 and H4 to bind the CoA peptide despite bigelovin demonstrating antagonist behavior by repressing wild-type RXRα basal transactivation activity in a reporter assay (Ref. [102]). In 1G1U, H12 of each monomer of the tetramer formed a surface with helices H3 and H4 of the monomer from the opposing homodimer to repress transactivation.…”

Section: Figurementioning

confidence: 99%

See 3 more Smart Citations

The retinoid X receptors and their ligands

Dawson

Xia

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

321

325

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This chapter presents an overview of the current status of studies on the structural and molecular biology of the retinoid X receptor subtypes α, β, and γ (RXRs, NR2B1–3), their nuclear and cytoplasmic functions, post-transcriptional processing, and recently reported ligands. Points of interest are the different changes in the ligand-binding pocket induced by variously shaped agonists, the communication of the ligand–bound pocket with the coactivator binding surface and the heterodimerization interface, and recently identified ligands that are natural products, those that function as environmental toxins or drugs that had been originally designed to interact with other targets, as well as those that were deliberately designed as RXR-selective transcriptional agonists, synergists, or antagonists. Of these synthetic ligands, the general trend in design appears to be away from fully aromatic rigid structures to those containing partial elements of the flexible tetraene side chain of 9-cis-retinoic acid.

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“…Shen and coworkers reported the structure (3OZJ) of the dimeric bigelovin–RXRα LBD–SRC-1 CoA peptide complex [102] (Fig. 7).…”

Section: Dimerizationmentioning

confidence: 99%

Section: Dimerizationmentioning

confidence: 99%

Section: Dimerizationmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

The retinoid X receptors and their ligands

Dawson

Xia

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

321

325

View full text Add to dashboard Cite

show abstract

“…It has been reported that bigelovin could also target the NF-κB and RXR pathways and trigger the proteolysis of E2F1 [41][42][43] . These targets are all relevant to cancer cell survival and growth.…”

Section: Discussionmentioning

confidence: 99%

Bigelovin inhibits STAT3 signaling by inactivating JAK2 and induces apoptosis in human cancer cells

et al. 2015

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Aim: To study the function and mechanism of bigelovin, a sesquiterpene lactone from the flower of Chinese herb Inula hupehensis, in regulating JAK2/STAT3 signaling and cancer cell growth. Methods: HepG2 cells stably transfected with the STAT3-responsive firefly luciferase reporter plasmid (HepG2/STAT3 cells), and a panel of human cancer cell lines were used to identify active compounds. Cell viability was measured using MTT assay. Western blotting was used to detect protein expression and phosphorylation. Kinase assays were performed and the reaction between bigelovin and thiolcontaining compounds was analyzed with LC-MS.

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Anti‐inflammatory effects of the petasin phyto drug Ze339 are mediated by inhibition of the STAT pathway

et al. 2017

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Ze339, an herbal extract from Petasites hybridus leaves is effective in treatment of allergic rhinitis by inhibition of a local production of IL-8 and eicosanoid LTB in allergen-challenged patients. However, the mechanism of action and anti-inflammatory potential in virally induced exacerbation of the upper airways is unknown. This study investigates the anti-inflammatory mechanisms of Ze339 on primary human nasal epithelial cells (HNECs) upon viral, bacterial and pro-inflammatory triggers. To investigate the influence of viral and bacterial infections on the airways, HNECs were stimulated with viral mimics, bacterial toll-like-receptor (TLR)-ligands or cytokines, in presence or absence of Ze339. The study uncovers Ze339 modulated changes in pro-inflammatory mediators and decreased neutrophil chemotaxis as well as a reduction of the nuclear translocation and phosphorylation of STAT molecules. Taken together, this study suggests that phyto drug Ze339 specifically targets STAT-signalling pathways in HNECs and has high potential as a broad anti-inflammatory drug that exceeds current indication. © 2016 BioFactors, 43(3):388-399, 2017.

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Structure Basis of Bigelovin as a Selective RXR Agonist with a Distinct Binding Mode

Cited by 35 publications

References 42 publications

The retinoid X receptors and their ligands

The retinoid X receptors and their ligands

Bigelovin inhibits STAT3 signaling by inactivating JAK2 and induces apoptosis in human cancer cells

Anti‐inflammatory effects of the petasin phyto drug Ze339 are mediated by inhibition of the STAT pathway

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