生物活性

• 靶点	STAT3 IC50:4.6μM

• 描述STAT3, the protein most linked to tumorigenesis in STAT family and regarded as a target for cancer therapy, is constitutively activated in most human solid tumors and is involved in the proliferation, angiogenesis, immune evasion, and anti-apoptosis of cancer cells. Cryptotanshinone, isolated from the roots of Salvia miltiorrhiza Bunge (Danshen), is a STAT3 inhibitor with IC50 of 4.6μM for inhibition of STAT3 activity of HCT-116 cells in luciferase assay. The STAT3 activity could be inhibited by 7μM cryptotanshinone in MDA-MB-231, HeLa, DU 145, and HCT-116 cells after 24-h treatment in luciferase assay. Cryptotanshinone could attenuated phosphorylation level of STAT3 at Tyr705 site in DU145 cells in a dose (5-10μM, 24h)- and time (7μM, 0.25-4h)-dependent manner, with suppression of JAK2 phosphorylation as a secondary effect of cryptotanshinone treatment, but showed inhibition of STAT3 at Ser727 site at concentration of 10μM. Dose-dependent inhibition of expression of STAT3-targeted proteins, including cyclin D1, surviving and Bcl-xL, could be observed in DU145 cells treated with 5-10μM Cryptotanshinone. Accumulation of cell cycle G0-G1 phase can be induced by Cryptotanshinone at 7 or 10μM, and increased apoptosis could be observed in DU145 cells treated with 15μM. Cryptotanshinone at concentration of 7μM could selectively inhibited growth inhibition of DU145 prostate cancer cell line that expressing constitutively active STAT3 time-dependently in 12-96h, but not cells lack constitutively active STAT3 such as PC3 and LNCaP. Cryptotanshinone can colocalize with STAT3 molecules in the cytoplasm and inhibit the formation of STAT3 dimers. Intraperitoneal injection with 50mg/kg Cryptotanshinone inhibited the growth of human colon tumor xenograft in nude mice.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  human AGS cells	-	Function assay	16 h	Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay, IC50=1.58 μM	17583950
  human AGS cells	-	Growth inhibition assay	24 h	Viability of human AGS cells under hypoxic conditions after 24 hrs by MTT assay, IC50=10.2 μM	17583950
  human HCT116 cells	-	Function assay	24 h	Inhibition of STAT3 expressed in human HCT116 cells after 24 hrs by luciferase reporter gene assay, ic50=4.6 μM	22650325

• 更多

• 动物研究
  剂量	Rat: 5.7 mg/kg[3] (p.o.), 60 mg/kg[4] (i.v.); 17.8 mg/kg - 1080 mg/kg[4] (p.o.) Ob/ob mice: 200 mg/kg - 600 mg/kg[2] (p.o.) Dog: 53.4 mg/kg[4] (i.v.)
  给药途径	p.o., i.v.
  动物药代数据	Animal Rats[3] Dose 5.7 mg/kg Administration i.g. t1/2λz 170.5 ± 30.3 min CLλz/F 3.6 ± 1.5 l/(min·kg) Tmax 33.3 ± 8.2 min Cmax 6.5 ± 2.2 g/l AUC0→∞ 2595.8 ± 394.8 g/(min·l) AUC0→t 2553.4 ± 399.8 g/(min·l)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01452477	Polycystic Ovary Syndrome	Not Applicable	Unknown	July 2014	China, Heilongjiang ... more >> Heilongjiang University of Chinese Medicine Recruiting Harbin, Heilongjiang, China, 150040 Contact: Wenjuan Shen, doctor    +86-045182118464    shenwenjuankx@163.com    Contact: Yuehui Zhang, doctor    +86-045182118464    manbingPCOS@163.com    Principal Investigator: Wenjuan Shen, doctor          China, Jiangsu Huaian Maternal and Child Health Hospital Recruiting Huaian, Jiangsu, China, 223001 Contact: Huiying Xue, Scholar    +8613505238015    haxuehuiying@126.com    Principal Investigator: Huiying Xue, bachlor          Lianyungang Maternal and Child Health Hospital Active, not recruiting Lianyungang, Jiangsu, China, 222000 China, Jiangxi JiangXi University of Traditional Chinese Medicine Completed Nanchang, Jiangxi, China, 330000 Collapse <<

• 参考文献

• [1] Shin DS, Kim HN, et al. Cryptotanshinone inhibits constitutive signal transducer and activator of transcription 3 function through blocking the dimerization in DU145 prostate cancer cells. Cancer Res. 2009 Jan 1;69(1):193-202.

  [2] Kim EJ, Jung SN, et al. Antidiabetes and antiobesity effect of cryptotanshinone via activation of AMP-activated protein kinase. Mol Pharmacol. 2007 Jul;72(1):62-72.

  [3] Song M, Hang TJ, et al. Effects of the coexisting diterpenoid tanshinones on the pharmacokinetics of cryptotanshinone and tanshinone IIA in rat. Eur J Pharm Sci. 2007 Dec;32(4-5):247-53. Epub 2007 Aug 15.

  [4] Pan Y, Bi HC, et al. Pharmacokinetic characterization of hydroxylpropyl-beta-cyclodextrin-included complex of cryptotanshinone, an investigational cardiovascular drug purified from Danshen (Salvia miltiorrhiza). Xenobiotica. 2008 Apr;38(4):382-98.