生物活性

Triptolide inhibits DNA-dependent ATPase activity of XBP and induces inhibition of RNA polymerase II (RNAPII)-mediated transcription (IC50 = 200 nM). Blocks RNA synthesis in HeLa cells (IC50 = 62 nM); exhibits potent antiproliferative activity in 60 cancer cell lines (average IC50 = 12 nM) and induces apoptosis by blocking TNF-α-mediated c-IAP1 and c-IAP2 induction. Triptolide has been shown to induce apoptosis of T lymphocytes by activating caspases, displaying an increase of DEVD-cleavable caspase activity correlated with the apoptosis. The proliferation of rheumatoid synovial fibroblasts characteristic of rheumatoid arthritis was similarly suppressed by treatment with Triptolide through an increase in caspase-3 activity. Cytokine gene expression in blood lymphocytes and T-cells are also suppressed by Triptolide, blocking the transcriptional activation of purine-box/antigen receptor response element/nuclear factor of activated T-cells (NF-AT) and of NF-kappaB. Also displays immunosuppressive and anti-inflammatory activity.

体外研究

体内研究

激酶实验

细胞实验

Cells

MCF-7 cells were were cultured in phenolred-free medium.

AntiproliferativeActivity

Antiproliferative activity was determined usingthe colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide(MTT) method. Cells were grown on tissue culture flasks in Dulbecco’s ModifiedEagle’s Medium (DMEM) containing 10% heat-inactivated fetal bovine serum (FBS) andantibiotics (100 U/ml penicillin G, 100μg/mlstreptomycin) at 378C in 5% CO₂ and 95% air in a humidified incubator.At the start of the experiment, the cell suspension at a density of 1 3 105 wastransferred to 96-well microplates (180μl/well).After 24 h of cell culture, the medium was replaced by 10% dextrancharcoal(DCC) treated FBS which containing 10, 50, and 100 nM triptolide, 1 nM of E2alone or the combination of triptolide and E2 for 24, 48, and 72 h,respectively. At the end of treatment period, 20 mL of MTT reagent (5 mg/ml inPBS) was added to each well. The plates were then incubated for 4 h at 37^oCin the dark. The medium was removed and MTT reduction product (formazancrystals) was dissolved in Dimethyl Sulfoxide (DMSO), and the absorbance at 570nm was measured with an ELISA reader.

动物实验

Xenograft tumor model

Six-week-old NOD.CB17 Prkdcscid/J mice weremaintained in a microisolator in pathogen-free conditions. The mice weredivided into four groups; each mouse in each group (n = 5; 5-FU, n = 3) wassubcutaneously injected with 2 × 10⁶ of both SAS and SAS coculturedwith macrophage-like U937 cells. Three days later, the mice in each group werefurther treated with triptolide (TPL) (0.15 mg/kg/day) and 5-FU (12 mg/kg/day),and a vehicle control (PBS) was then separately administered to the groupsthrough intraperitoneal (ip) injection. The size of the transplanted tumors wasmeasured using gauged calipers twice a week, and the tumor volume wascalculated using the following formula: volume (V) = 1/2 × (length × width2).At the end of the treatment, the mice were sacrificed, and the tumors wereremoved, weighed, and photographed.

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Qiu, D., et al. 1999. J. Biol. Chem. 274: 13443-13450.
[2] Kusunoki, N., et al. 2004. BMC Pharmacol. 4 :2.
[3] Liacini, A., et al. 2005. Biochem. Biophys. Res. Commun. 327: 320-327.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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