Romidepsin-FK-228-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERomidepsinCat. No.: HY-15149CAS No.: 128517-07-7Synonyms: FK 228; FR 901228; NSC 630176分式: CHNOS分量: 540.7作靶点: HDAC作通路: Cell Cycle/DNA Damage; Epigenetics储存式: Powder -20C 3 years* 该产品在溶液状态不稳定，建议您现现配，即刻使。溶解性数据体外实验 DMSO : 50 mg/mL

2、(92.47 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.8495 mL 9.2473 mL 18.4945 mL5 mM 0.3699 mL 1.8495 mL 3.6989 mL10 mM 0.1849 mL 0.9247 mL 1.8495 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；该产品在溶液状态不稳定，建议您现现配，即刻使。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，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建

3、议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.85 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.62 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubili

4、ty: 2.5 mg/mL (4.62 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Romidepsin种有效的 HDAC1 和 HDAC2 抑制剂，IC50 值分别为 36 nM 和 47 nM。IC50 & Target HDAC1 HDAC2 HDAC4 HDAC636 nM (IC50) 47 nM (IC50) 510 nM (IC50) 14000 nM (IC50)体外研究 Romidepsin potently inhibits HDAC1

5、and HDAC2 (IC50=36, 47 nM, respectively). Romidepsin has slightlyinhibitory effects against HDAC4 and HDAC6 (IC50=510, 14000 nM, respectively). Romidepsin induceshistone acetylation and p21 expression with an EC50 of 3.0 nM. Romidepsin is more strongly than redFKwith EC50 of 11 nM due to the instabi

6、lity of redFK in HeLa cells 1. Romidepsin is 100 times more potentthan TSA and 1,000,000 times more potent than butyrate in inhibiting the proliferation of the A549 cells.Romidepsin causes mitotic arrest, and that the treatment with HDIs causes defects in chromosomesegregation in mitosis 2. Romideps

7、in inhibits the growth of U-937, K562, and CCRF-CEM cells with IC50values of 5.92 nM, 8.36 nM, and 6.95 nM, respectively 3.体内研究 In a scid mouse lymphoma model, romidepsin treated mice once or twice a week survive longer than controlmice, with median survival times of 30.5 (0.56 mg/kg) and 33 days (0

8、.32 mg/kg), respectively (vs. 20 days incontrol mice). Remarkably, 2 out of 12 mice treated with romidepsin (0.56 mg/kg once or twice a week)survive past the observation period of 60 days. The apoptotic population of U-937 cells increases to 37.7%after 48 hr of treatment with romidepsin in a time de

9、pendent manner. In addition, romidepsin induces G1 andG2/M arrest and the differentiation of U-937 cells to the CD11b(+)/CD14(+) phenotype. Expression ofp21(WAF1/Cip1) and gelsolin mRNA increases up to 654- and 152-fold, respectively, after 24 hr of treatmentwith romidepsin. Romidepsin causes histon

10、e acetylation in p21(WAF1/Cip1) promoter regions, including theSp1-binding sites 3.PROTOCOLKinase Assay 1 For the enzyme assay, 10 L of 3Hacetyl-labeled histones (25,000 cpm/10 g) are added to 90 L of theHDAC enzyme fraction extracted from 293T cells overexpressing HDAC1 or HDAC2 in the presence ofi

11、ncreasing concentrations of Romidepsin, and the mixture is incubated at 37C for 15 minutes. The enzymereaction is linear for at least 1 hour. The reaction is stopped by the addition of 10 L of concentrated HCl.The released 3Hacetic acid is extracted with 1 mL of ethylacetate, and 0.9 mL of the solve

12、nt layer is takeninto 5 mL of aqueous counting scintillant II solution for determination of radioactivity. The IC50 values aredetermined from at least three independent dose-response curves.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Ce

13、lls are exposed to various concentrations of Romidepsin for 72 hours in 96-well plates. 20 L of 5 mg/mLMTT solution in PBS is added to each well for 4 hours. After removal of the medium, 170 L of DMSO isadded to each well to dissolve the formazan crystals. The absorbance at 540 nm is determined. In

14、addition,cells are incubated with trypan blue, and the numbers of blue (dead) cells and transparent (live) cells arecounted in a hemocytometer. For cell cycle analysis, cells are incubated for 30 minutes in propidium iodide2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEstaining solution containing

15、 0.05 mg/mL propidium iodide, 1 mM EDTA, 0.1% Triton X-100, and 1 mg/mLRNase A in PBS. The suspension is then passed through a nylon mesh filter and analyzed on a BectonDickinson FACScan.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Briefly, ma

16、le scidmice are injected i.p. with 150 mg/kg of cyclophosphamide. All the mice injected withAdministration 3 cyclophosphamide alone survive over the observation period. Twenty-four hours after cyclophosphamideinjection, mice are inoculated i.p. with 1107 U-937 cells in 500 L PBS. Twenty-four hours a

17、fter tumor cellinoculation, the mice are treated i.p. with or without FK228 at doses ranging from 0.1 to 1 mg/kg, once ortwice a week. Control mice are treated with 10% HCO60 saline twice a week. Six and twelve mice are usedfor FK228-treated and control groups, respectively. The observation period i

18、s 60 days after cell inoculation,and the antitumor effect is evaluated by survival time, which is analyzed for statistical significance by Petostest.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 Cancer Res. 2016 Dec 1;76(23):7001-7011. PLo

19、S Pathog. 2018 Sep 13;14(9):e1007267. J Med Chem. 2015 Nov 12;58(21):8638-46. ACS Med Chem Lett. 2018 Feb 6;9(3):268-273. J Pharmacol Exp Ther. 2019 Jul 15. pii: jpet.119.258129.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Furumai R, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I