隐丹参酮作用机制 - Medchemexpress - MCE中国

1、Product Data SheetCryptotanshinoneCat. No.: HY-N0174CAS No.: 35825-57-1分式: CHO分量: 296.36作靶点: STAT; Autophagy作通路: JAK/STAT Signaling; Stem Cell/Wnt; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 5 mg/mL (16.87 mM; Need ultrasonic)SolventMass1 mg 5 mg

2、10 mgConcentration制备储备液1 mM 3.3743 mL 16.8714 mL 33.7427 mL5 mM 0.6749 mL 3.3743 mL 6.7485 mL10 mM 0.3374 mL 1.6871 mL 3.3743 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In V

3、itro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.83 mg/mL (2.80 mM); Suspended solution; Need ultrasonic此案可获得 0.83 mg/mL (2.80 mM) 的均匀悬浊液，悬浊液可于服

4、和腹腔注射。以 1 mL 作液为例，取 100 L 8.3 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.83 mg/mL (2.80 mM); Clear solution此案可获得 0.83 mg/mL (2.80 mM，饱和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液为例，取 100 L 8.

5、3 mg/mL 的澄均匀。DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 0.83 mg/mL (2.80 mM); Clear solution此案可获得 0.83 mg/mL (2.80 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 8.3 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Cryptotanshinone是从丹参的根中提取的天

6、然化合物，具有抗肿瘤活性。 Cryptotanshinone抑制 STAT3 的 IC50 为4.6 M。IC & Target STAT34.6 M (IC50)体外研究 Cryptotanshinone significantly inhibits STAT3-dependent luciferase activity, the STAT3 Tyr705 phosphorylation andthe dimerization of STAT3, compared to tanshinone IIA which exhibits no activity. Cryptotanshinone (

7、7 M)dramatically blocks STAT3 Tyr705 phosphorylation but not STAT3 Ser727 phosphorylation in DU145 cells, andsignificantly inhibits JAK2 phosphorylation with IC50 of appr 5 M without affecting the phosphorylation of upstreamkinases c-Src and EGFR, suggesting the inhibition of STAT3 Tyr705 phosphoryl

8、ation might due to a direct mechanismprobably by binding to the SH2 domain of STAT3. Cryptotanshinone significantly inhibits the proliferation of DU145prostate cancer cells harboring constitutively active STAT3 with GI50 of 7 M by blocking STAT3 activity, which leadsto the down-regulation of cyclin

9、D1, Bcl-xL, and survivin, subsequently the accumulation in the G0-G1 phase.Cryptotanshinone exhibits less growth inhibitory effect on PC3, LNCaP and MDA-MB-468 cells1. Cryptotanshinonesignificantly attenuates the in vitro hormonal effects of DEX on ovaries, as indicated by a significant decrease in

10、T andan increase in P levels in the culture medium. Cryptotanshinone significantly increases the levels of phosphorylatedAKT2 and GSK3 in the DEX-treated ovaries2. Cotreatment with imatinib and Cryptotanshinone shows a significantsynergistic killing effect in both imatinib sensitive and resistant CM

11、L cell lines, as well as primary CML cells3.体内研究 Cryptotanshinone reverses the ovarian IR and significantly increases 2-deoxy-D-1,2-3H-glucose uptake in all examined tissues from the DEX-treated mice. Cryptotanshinone significantly reduces the ovulation rate and plasma E2 and P levels2. Cryptotanshi

12、none administration significantly reduces the body weight and food intake of ob/ob mice(C57BL/6J-Lepob) and diet-induced obese (DIO) mice in a dose-dependent manner. Cryptotanshinone causesnoticeably less fat in the adipose tissues, significant reductions of serum triglycerides and cholesterol level

13、s, and 2.5-to 3-fold higher AMPK activity of the skeletal muscles than in the control mice. Oral administration ofCryptotanshinone at 600 mg/kg/day produces dramatic reductions in blood glucose levels of ob/ob mice (C57BL/6J-Lepob), db/db mice (C57BL/KsJ-Leprdb), and ZDF rats, which occur after 3 da

14、ys and persist over the entirety of themonitoring period4.PROTOCOLKinase Assay 1 HCT-116 cells are transiently transfected with reporter plasmid having the STAT3-binding element for regulatingluciferase assay. Cells are treated with Cryptotanshinone for 24 hours at a concentration range of 0.2 to 50

15、 M. Aftertreatment, cells are harvested in 20 L of passive lysis buffer and luciferase activity is evaluated by the Dual LuciferaseReporter Assay kit on Wallac Victor2. The concentration of Cryptotanshinone that inhibits the luciferase activity by50% represents IC50 value.MCE has not independently c

16、onfirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemECell Assay 3 The MTT assay is used for the assessment of cell growth inhibition as described previously. Cells are seeded at adensity of 8000 cells per well in 96-well plates in RPMI-1640 containing 10% FBS.

17、Different concentrations of imatiniband CPT are added and incubated for another 24 h. Then, 20 L of MTT are added into each well and the absorbanceat 570 nm is measured on an enzyme linked immunosorbent assay (ELISA) plate reader. The coefficient of druginteraction (CDI) between imatinib and CPT is

18、determined according to a previous study. The calculated method is asfollows: CDI/AB/(A B). According to the absorbance of each group, AB is the ratio of the combination group to thecontrol group; A or B is the ratio of the single agent group to the control group. CDI 1 indicates an antagonistic eff

19、ect. In the combination treatment group, theconcentrations of CPT are arbitrarily designated according to the 50% inhibitory concentration (IC50) value. Then, thecell viabilities are determined after treatment with different concentrations of imatinib plus CPT (constant CPTconcentration for one cell

20、 type). Finally, the combination IC50 values of imatinib are calculated, and are represented inTable I. The primary CML cells CP1 to CP3 are isolated from patients in chronic phase, while BC1 and BC2 are isolatedfrom patients in blast crisis. Three independent sets of experiments are performed. The

21、IC50 values are presented asthe meanstandard deviation (SD).MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 J Pineal Res. 2019 Apr;66(3):e12552. Cell Death Dis. 2020 May 1;11(5):304. PLoS Genet. 2015 Mar 27;11(3):e1005120. J Cell Mol Med. 20

22、17 Sep;21(9):2172-2183. J Virol. 2019 Dec 4. pii: JVI.01384-19.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Shin DS, et al. Cryptotanshinone inhibits constitutive signal transducer and activator of transcription 3 function through blocking the dimerization inDU145 prostate cancer cells. Cancer Res. 2009 Jan 1;69(1):193-202.2. Huang Y, et al. Cryptotanshinone reverses ovarian insulin