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Wilforine Sale

(Synonyms: 雷公藤次碱) 目录号 : GC30494

Wilforine (WR), a sesquiterpene pyridine alkaloid found in T. wilfordii plants, significantly inhibits the efflux activity of P-glycoprotein (P-gp).

Wilforine Chemical Structure

Cas No.:11088-09-8

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10mM (in 1mL DMSO)
¥1,460.00
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1mg
¥452.00
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5mg
¥930.00
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10mg
¥1,530.00
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产品描述

Wilforine (WR), a sesquiterpene pyridine alkaloid found in T. wilfordii plants, significantly inhibits the efflux activity of P-glycoprotein (P-gp).

[1] Ying-Tzu Chang, et al. Phytomedicine. 2020 Jun;71:153239.

Chemical Properties

Cas No. 11088-09-8 SDF
别名 雷公藤次碱
Canonical SMILES CC(OCC(C1OC(C)=O)(C(C(OC(C2=CC=CC=C2)=O)C3OC(C4C)=O)OC(C)=O)C(OC(C)(COC(C5=CC=CN=C5CC4)=O)C6C1OC(C)=O)(C3(O)C)C6OC(C)=O)=O
分子式 C43H49NO18 分子量 867.85
溶解度 DMSO: 50 mg/mL (57.61 mM) 储存条件 Store at -20°C
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1 mg 5 mg 10 mg
1 mM 1.1523 mL 5.7614 mL 11.5227 mL
5 mM 0.2305 mL 1.1523 mL 2.3045 mL
10 mM 0.1152 mL 0.5761 mL 1.1523 mL
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Research Update

Wilforine

Wilforine resensitizes multidrug resistant cancer cells via competitive inhibition of P-glycoprotein

Background and purpose: Multidrug resistance (MDR) remains the main obstacle in cancer treatment and overexpression of P-glycoprotein (P-gp) is one of the most common causes of chemoresistance. The development of novel P-gp inhibitors from natural products is a prospective strategy to combat MDR cancers. Among the natural sesquiterpene compounds, sesquiterpene pyridine alkaloids exhibit various biological properties. Therefore, in the present study, we evaluated the modulatory effects of wilforine on P-gp expression and function. The molecular mechanisms and kinetic models of wilforine-mediated P-gp inhibition were further investigated.
Methods: The human P-gp stable expression cells (ABCB1/Flp-InTM-293) and human cervical cancer cells (sensitive: HeLaS3; MDR: KBvin) were used. The cell viability was assessed by SRB assay. The inhibitory effect of wilforine on P-gp efflux and the underlying mechanism were evaluated by assays for calcein-AM uptake, rhodamine123 and doxorubicin efflux, ATPase activity, real-time quantitative RT-PCR, apoptosis, and cell cycle analysis. Molecular docking was performed by the docking software CDOCKER with BIOVIA Discovery Studio 4.5 (D.S. 4.5).
Results: We found that wilforine significantly inhibited the efflux activity of P-gp in a concentration-dependent manner. Further kinetic analysis demonstrated that wilforine significantly inhibited P-gp efflux function by competitive inhibition and stimulated the basal P-gp ATPase activity. In addition, wilforine re-sensitized MDR cancer cells to chemotherapeutic drugs. The docking model indicated that wilforine was bound to residues of P-gp such as LEU884, LYS887, THR176 and ASN172.
Conclusion: These results suggest a novel future therapeutic strategy for MDR cancer using wilforine as an adjuvant treatment with chemotherapy.

Wilforine, the Q-marker and PK-maker of Tripterygium glycosides tablet: Based on preparation quantitative analysis and PK-PD study

Background: The quality standard of Tripterygium glycosides tablet (TGT) by CFDA can not fully reflect the effectiveness and safety. While, Q-marker was proposed to solve the problem of traditional Chinese medicine. PK-marker is mainly used to reflect the material exposure and the influencing factors of Chinese medicine after administration.
Purpose: Based on the study of quantitative analysis, cytotoxicity and pharmacokinetics, this study screened out and confirmed whether wilforine could be served as a potential Q-marker and PK-marker of TGT.
Methods: A sensitive and selective UPLC-MS/MS method was developed and applied to quantitative research of TGT preparation and pharmacokinetics study of TGT. Then, HepG2 cells assay was used to evaluate the cytotoxicity induced by alkaloids in TGT. Then, a PK-PD research was carried out in adjuvant arthritis (AA) rats and control rats after oral administration of TGT, with different dosage and timing. The pharmacokinetic characteristics were determined and calculated by DAS1.0. The pharmacodynamics of TGT was evaluated by the change of paw swelling through one-way ANOVA analysis.
Results: The quality of four alkaloids showed significant difference among four manufacturers, and they were abundant component in TGT from three manufacturers of all. HepG2 cells test revealed that wilforine and wilforgine could induce the cytotoxicity obviously. Pharmacodynamics index suggested that TGT had therapeutic effect on adjuvant arthritis. Thus, the four cases of death occurred in the high dose AA rat group had proven the significant toxicity caused by continuous high dose TGT administration. Furthermore, the result of pharmacokinetic study proved that Cmax, and AUC(0-tn) of wilforine have dose-dependent and time-dependent characteristics. But for wilforgine, there was no indication that there was an accumulation phenomenon in vivo and its plasma concentration showed low exposure. Therefore, it could hardly become the PK-marker of TGT.
Conclusion: Wilforine is proposed as a biologically active and toxic component of TGT that can be served both as Q-marker and PK-marker. The quality, clinical safety, and efficacy of TGT should be evaluated by the quality of wilforine.

Effect of Wilforine on the Calcium Signaling Pathway in Mythimna separata Walker Myocytes Using the Calcium Imaging Technique

Although the action site of wilforine is located in the muscle tissue of insects, the insecticidal mechanism of wilforine is not yet clear. This research explored the effects of wilforine on the calcium signaling pathway using the calcium imaging technique to reveal the insecticidal mechanism. It was confirmed that wilforine had strong cytotoxicity to Mythimna separata myocytes with the IC50 values of 25.14 and 19.65 mg/L using CCK-8 and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods, respectively. The morphological development of M. separata myocytes was also affected. The calcium imaging technique showed that the intracellular calcium ion concentration ([Ca2+]i) increased by 23.45% of the initial value after being treated with 100 nM wilforine. However, wilforine did not increase [Ca2+]i after the myocytes were preincubated with thapsigargin, and the [Ca2+]i could not be decreased by 50 μM ryanodine after being treated with 100 nM wilforine. These results indicated that the targets of wilforine are located in the sarcoplasmic reticulum, and ryanodine receptor (RyR) is an important action target of wilforine. Furthermore, wilforine can also activate the inositol triphosphate receptor (IP3R), which was confirmed through the use of 2-aminoethyl diphenylborinate, an inhibitor of IP3R. Connected with previous research studies, it can be concluded that wilforine affects the calcium signaling pathway by combining with RyR and IP3R, causing calcium dyshomeostasis, which results in insect paralysis and death.

Insecticidal action of the botanical insecticide wilforine on Mythimna separata (Walker) related with the changes of ryanodine receptor expression

The detailed molecular mechanism of wilforine, a novel botanical insecticidal component, remains unclear, except for the knowledge that it affects the calcium signaling pathway. The aim of the current study was to examine the underlying molecular mechanism of wilforine in Mythimna separata (Walker) by transcriptome and RNA interference (RNAi), with chlorantraniliprole as control. RNA sequencing showed that the relative expression of genes related to the calcium signaling pathway and muscle contraction in M. separata treated with wilforine significantly changed and was further validated by qRT-PCR. Interestingly, the expression level of the ryanodine receptor (MsRyR) gene was downregulated by wilforine at relatively high concentrations and long treatment time, contrary to that observed using chlorantraniliprole. Furthermore, a putative MsRyR was cloned using a 16,258-bp contiguous sequence containing a 308-bp 5'-untranslated region and 578-bp 3'-untranslated region by RT-PCR and RACE. The results of the RNAi experiment showed that injection of dsMsRyR significantly reduced MsRyR mRNA levels, and growth and development were inhibited. Importantly, silencing of the MsRyR gene resulted in decreased susceptibility to both wilforine and chlorantraniliprole. Together with the results of our previous studies on toxic symptoms and muscle tissue lesions between wilforine and chlorantraniliprole, we propose that RyR Ca2+ release channel dysfunction is closely related with significant lethal mechanisms of wilforine.