Identification of Picrasidine C as a Subtype-Selective PPARα Agonist.

@article{Zhao2016IdentificationOP,
  title={Identification of Picrasidine C as a Subtype-Selective PPAR$\alpha$ Agonist.},
  author={Shuai Zhao and Yuichiro Kanno and Wei Li and Tatsunori Sasaki and Xiangyu Zhang and Jian Wang and Maosheng Cheng and Kazuo Koike and Kiyomitsu Nemoto and Huicheng Li},
  journal={Journal of natural products},
  year={2016},
  volume={79 12},
  pages={
          3127-3133
        }
}
Picrasidine C (1), a dimeric β-carboline-type alkaloid isolated from the root of Picrasma quassioides, was identified to have PPARα agonistic activity by a mammalian one-hybrid assay from a compound library. Among the PPAR subtypes, 1 selectively activated PPARα in a concentration-dependent manner. Remarkably, 1 also promoted PPARα transcriptional activity by a peroxisome proliferator response element-driven luciferase reporter assay. Furthermore, 1 induced the expression of PPARα-regulated… 
Computational investigation reveals Picrasidine C as selective PPARα lead: binding pattern, selectivity mechanism and ADME/tox profile
TLDR
The detailed information of binding pattern and affinity for Picrasidine C elucidated here will be valuable for chemical modification and for finding more potent, safe and selective PPARα agonists during structural optimization.
Evolution of a 4-Benzyloxy-benzylamino Chemotype to Provide Efficacious, Potent, and Isoform Selective PPARα Agonists as Leads for Retinal Disorders.
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P proof-of-concept in vivo efficacy in an STZ-induced vascular leakage model (rat) and preliminary pharmacokinetic assessment of a first-generation lead 4a (A91) are reported and a pipeline of candidates positioned for detailed PK/PD and pre-clinical evaluation is identified.
Anticancer effects of picrasidine I on oral squamous cell carcinoma
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Analysis of MAPK signaling pathway revealed that picrasidine I‐mediated proapoptotic activities by downregulating JNK phosphorylation is identified as a potent anticancer agent that can be used as a therapeutic intervention against oral squamous cell carcinoma.
Picrasidine I from Picrasma Quassioides Suppresses Osteoclastogenesis via Inhibition of RANKL Induced Signaling Pathways and Attenuation of ROS Production
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It is demonstrated that PI has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-κB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.
FGFR2 regulation by picrasidine Q inhibits the cell growth and induces apoptosis in esophageal squamous cell carcinoma
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The results are the first to identify that PQ might be a chemopreventive and chemotherapeutic agent by direct targeting FGFR2 and inhibiting cell proliferation of ESCC cells.
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References

SHOWING 1-10 OF 39 REFERENCES
Picrasidine N Is a Subtype-Selective PPARβ/δ Agonist.
TLDR
The naturally occurring dimeric alkaloid picrasidine N from Picrasma quassioides was identified as a novel PPARβ/δ agonist from a library consisting of plant extracts and natural compounds using a mammalian one-hybrid assay, and this compound was characterized.
Inhibition of peroxisome-proliferator-activated receptor (PPAR)alpha by MK886.
TLDR
Results show that MK886 can inhibit PPARalpha, making it the first compound identified to have such an effect, and may indicate that PPAR alpha is not directly involved in MK886-induced apoptosis.
Novel indole-based peroxisome proliferator-activated receptor agonists: design, SAR, structural biology, and biological activities.
TLDR
In vitro evaluation led to identification of a novel series of indole compounds with a benzisoxazole tail as potent PPAR agonists with the lead compound 14 displaying an excellent pharmacokinetic profile in BALB/c mice and an efficacious glucose lowering activity in KKA(y) mice.
Discovery of an oxybenzylglycine based peroxisome proliferator activated receptor alpha selective agonist 2-((3-((2-(4-chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic acid (BMS-687453).
An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) alpha agonist, with an EC(50) of 10 nM for human
Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis.
PPARs: therapeutic targets for metabolic disease.
Peroxisome Proliferator-Activated Receptor Alpha Target Genes
TLDR
An overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPAR α target genes is presented.
Effects of Fibrate Drugs on Expression of ABCA1 and HDL Biogenesis in Hepatocytes
TLDR
It is concluded that fibrates enhance expression of ABCA1 in hepatocytes to contribute to increase of the HDL biogenesis in a PPAR-dependent manner, whether exclusively or nonexclusively on PPARα.
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