生物活性

• 靶点	XIAP IC50:4.1μM

• 描述Embelin is a potent XIAP inhibitor with IC50 value of 4.1μM (measured by FP-based biochemical binding assay) ^[1]. Pretreatment with embelin 12h prior to TNFα at concentration ranging in 10-50μM can dose-dependently inhibit TNFα-induced NF-κB activation by inhibiting IκB degradation, as well as inhibted TNFα-induced p65 nuclear translocation due to inhibition of p65 phosphorylation in KBM-5 cells. with no affect on protein level of IAP1, IAP2 and XIAP. Exposure to 50μM embelin for 6-24h could reduce the antiapoptotic proteins survivin, IAP1/2, and suppress Bcl-xL, cFLIP, and TRAF1, suppress the cell proliferation gene expression, including COX-2, cyclin D1 and c-Myc, as well as gene products involved in tumor metastasis, including VEGF, MMP-9 and ICAM-1, which were all TNF-induced NF-κB-dependent^[2]. The induction of autophagic and apoptotic cell death by embelin can also be observed in human oral squamous cell carcinoma Ca9-22 cell line^[3]. Neonatal injections of 20mg/kg embelin, s.c., could exacerbate hypoxia-ischemia-induced persistent behavioral deficits in female rats on postnatal day 7, but not in male rats^[4].
• 作用机制Embelin bind to the XIAP-BIR3 domain where caspase-9 and Smac proteins bind. ^[1]

• 动物研究
  剂量	Rat: min = 15 mg/kg, max = 120 mg/kg[5] (p.o.); 5 mg/kg[5] (i.v.); 0.3 mg/kg - 1.2 mg/kg[6] (i.p.)
  给药途径	p.o., i.v., i.p.
  动物药代数据	Animal Rats[5] Dose 5 mg/kg (i.v.) 15 mg/kg (p.o.) Administration i.v. p.o. AUC0→24h 2.17 ± 0.49 μg/ml·h (i.v.) 1.97 ± 0.78 μg/ml·h (p.o.) MRT0→24 1.28 ± 0.11 h (i.v.) 1.49 ± 0.49 h (p.o.) T1/2 1.52 ± 0.83 h (i.v.) 1.01 ± 0.58 h (p.o.) Tmax 0.03 ± 0.00 h (i.v.) 0.71 ± 0.19 h (p.o.) Cmax 3.91 ± 1.34 μg/ml (i.v.) 1.05 ± 0.21 μg/ml (p.o.) AUC0→∞ 3.21 ± 0.62 μg/ml·h (i.v.) 2.92 ± 0.69 μg/ml·h (p.o.) MRT0→∞ 3.43 ± 0.41 h (i.v.) 3.21 ± 1.15 h (p.o.)