維替泊芬作用機制 - Medchemexpress - MCE中國

1、Product Data SheetVerteporfinCat. No.: HY-B0146CAS No.: 129497-78-5分式: CHNO分量: 718.79作靶點: YAP; Apoptosis; Autophagy作通路: Stem Cell/Wnt; Apoptosis; Autophagy儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數(shù)據(jù)體外實驗 DMF : 25 mg/mL (34.78 mM; Need ultrasonic)D

2、MSO : 8 mg/mL (11.13 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.3912 mL 6.9561 mL 13.9123 mL5 mM 0.2782 mL 1.3912 mL 2.7825 mL10 mM 0.1391 mL 0.6956 mL 1.3912 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; -20

3、C, 1 month (protect from light)。-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 Vitro 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% DMF 40% PEG300 5% Tween-80 45% saline2

4、.Solubility: 2.5 mg/mL (3.48 mM); Clear solution請依序添加每種溶劑： 10% DMF 90% (20% SBE-CD in saline)3.Solubility: 2.5 mg/mL (3.48 mM); Suspended solution; Need ultrasonic請依序添加每種溶劑： 10% DMF 90% corn oil4.Solubility: 2.5 mg/mL (3.48 mM); Clear solution; Need ultrasonic請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-

5、80 45% salineSolubility: 0.8 mg/mL (1.11 mM); Clear solution此案可獲得 0.8 mg/mL (1.11 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 8.0 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Page 1 of 2 www.MedChemE50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。5. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.8 m

6、g/mL (1.11 mM); Suspended solution; Need ultrasonic and warming此案可獲得 0.8 mg/mL (1.11 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 8.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。BIOLOGICAL ACTIVITY物活性 Verteporfin (CL 318952) 種于光動療法的光敏劑，于消除與年齡相關(guān)的 斑變性等疾病相關(guān)的眼內(nèi)異常管 。 Verteporfin 種 YAP 抑制劑，可破壞 YAP-TEA

7、D 相互作。Verteporfin 可以誘導(dǎo)細(xì)胞噬 (apoptosis)。 Verteporfin 種噬 (autophagy) 抑制劑，通過抑制噬體形成，在早期阻斷噬。IC & Target IC50: YAP-TEAD interaction體外研究 Verteporfin is specifically selected by PDX-cell screening. The concentrations to cause 50% growth inhibition (GI50) forPhLO, PhLH, and PhLK are 228 nM, 395 nM, and 538 nM

8、, respectively, whereas GI50 for ALL-1, TCC-Y/sr, and NPhA1are 3.93 M, 2.11 M, and 5.61 M, respectively. GSH significantly reduces the sensitivity of 2 out of 3 PDX cells toverteporfin. Verteporfin reduces the mitochondrial membrane potential in PDX cells1. Verteporfin reduces the PTX-resistance on

9、HCT-8/T cells by inhibiting YAP expression and combination therapy with verteporfin and NSC 125973shows synergism on inhibition of YAP and cytotoxicity to HCT-8/T2.體內(nèi)研究 Verteporfin (10 mg/kg, c.s.c.) and BMS-354825 significantly reduces the leukemia cell ratio, and combined therapyfurther reduced th

10、e number of leukemia cells in the spleen1.PROTOCOLCell Assay 1 PDX cells co-cultured with S17 cells are treated with 16 combinations of verteporfin (60 nM, 120 nM, 180 nM, and240 nM) and BMS-354825 (12 nM, 24 nM, 36 nM, and 48 nM). The viabilities of cells treated with each combinationare measured a

11、fter 48 h using FACS Aria flow cytometer. In order to estimate drug interaction between verteporfinand BMS-354825, a normalized isobologram and fraction affectedcombination index (CI) plot are made usingCompuSyn software. CI values greater than 1.0 indicated antagonistic effects, equal to 1.0 additi

12、ve effects, and below1.0 synergistic effects.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: PhLO cells (1.0107/mouse) are injected intravenously into 6-week-old male NOG mice, which are then treatedAdministration 1 with vehicle, verteporfi

13、n (140 mg/kg/day), BMS-354825 (20 mg/kg/day), and a combination of these drugs from days22 to 28. Verteporfin is administered by continuous subcutaneous infusion (c.s.c.) using Alzet osmotic pumps. Anintraperitoneal injection (i.p.) is performed for BMS-354825. All mice are sacrificed on day 28 and

14、the chimerism ofleukemia cells is investigated by flow cytometer using an anti-human CD19 antibody and antimouse CD45 antibody.Blood concentrations of verteporfin are calculated by LCMS-2020.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)Pag

15、e 2 of 3 www.MedChemE Cancer Cell. 2019 Sep 16;36(3):302-318.e7. Cell Res. 2020 Mar;30(3):229-243. Hepatology. 2019 Sep 11. Mol Cell. 2019 Jan 3;73(1):7-21.e7. Sci Adv. 2020 May 22.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Morishita T, et al. The photosensitize

16、r verteporfin has light-independent anti-leukemic activity for Ph-positive acute lymphoblastic leukemia andsynergistically works with BMS-354825. Oncotarget. 2016 Aug 2.2. Pan W, et al. Verteporfin can Reverse the NSC 125973 Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation throughInhibiting YAP Expression. Cell Physiol Biochem. 2016;39(2):481-90.3. Donohue E, et al. The autophagy inhibitor verteporfin moderately enhances the antitumor activity of gemcitabine ina pancreatic ductal adenocarcinoma model.J