隱丹參酮作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetCryptotanshinoneCat. No.: HY-N0174CAS No.: 35825-57-1分式: CHO分量: 296.36作靶點: STAT; Autophagy作通路: JAK/STAT Signaling; Stem Cell/Wnt; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 5 mg/mL (16.87 mM; Need ultrasonic)SolventMass1 mg 5 mg

2、10 mgConcentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In V

3、itro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.83 mg/mL (2.80 mM); Suspended solution; Need ultrasonic此案可獲得 0.83 mg/mL (2.80 mM) 的均勻懸濁液，懸濁液可于服

4、和腹腔注射。以 1 mL 作液為例，取 100 L 8.3 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.83 mg/mL (2.80 mM); Clear solution此案可獲得 0.83 mg/mL (2.80 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 8.

5、3 mg/mL 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.83 mg/mL (2.80 mM); Clear solution此案可獲得 0.83 mg/mL (2.80 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 8.3 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Cryptotanshinone是從丹參的根中提取的天

6、然化合物，具有抗腫瘤活性。 Cryptotanshinone抑制 STAT3 的 IC50 為4.6 M。IC & Target STAT34.6 M (IC50)體外研究 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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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