生物活性

• 描述Mebendazole is an antiparasitic which can bind nematode tubulin and cause inhibition of intestinal microtubule synthesis. It also inhibits Hh signaling, targeting SMO. Mebendazole was sufficient to reduce ShhN-induced expression of endogenous GLI1 and PTCH1 to basal levels at 0.1μM in the immortalized human retinal pigment epithelial cell line hTERT-RPE1. Similarly, there was partial reduction in GLI1 and PTCH1 transcripts at 0.1μM mebendazole and almost complete suppression at 1μM mebendazole, on the human medulloblastoma cell line DAOY. This inhibition of Hh signaling by Mebendazole led decrease of cell proliferation and survival, and increase apoptosis. Daily gavage of Mebendazole at dose of 50mg/kg for 38 days extended the median survival of DAOY orthotopic tumor xenograft mice. Mebendazole at 1μM decreased activation of SMO shown by the Gli-luc and Renilla reporter in NIH3T3 fibroblasts maintained in low-serum conditions for 48 hours. Mebendazole suppressed the formation of the primary cilium, a microtubule based organelle that functions as a signaling hub for Hh pathway activation. Combination of vismodegib and mebendazole resulted in additive Hh signaling inhibition.

• 动物研究
  剂量	Mice: 1 mg/kg - 50 mg/kg[2] (p.o.), 10 mg/kg- 100 mg/kg[3] (p.o.) Rat: 10 mg/kg[2] (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Dogs[4] Dose 500 mg tablet Administration Current hewable tablet AUC0→24h 221 ng·h/ml T1/2 2.072 h Tmax 9.90 h AUC0→31h 258 ng·h/ml Cmax 23.4 ng/ml AUC0→∞ 228 ng·h/ml