Antibodies
Romidepsin (FK228, Depsipeptide)
- 貨號 Cat. No.
- S3020
- 規格 Size
- 10mM/1mL~5mg
- 品牌 Brand
- Selleckchem
Description
Romidepsin (FK228, Depsipeptide)
Catalog No.S30205 Product Citations
Romidepsin (FK228, depsipeptide) is a potent HDAC1 and HDAC2 inhibitor with IC50 of 36 nM and 47 nM, respectively.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Romidepsin (FK228, depsipeptide) is a potent HDAC1 and HDAC2 inhibitor with IC50 of 36 nM and 47 nM, respectively. | |||||
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| Targets | HDAC1 | HDAC2 | ||||
| IC50 | 36 nM | 47 nM [1] | ||||
| In vitro | Unlike TSA, the active form redFK of Romidepsin strongly inhibits HDAC1 and HDAC2 with IC50 of 1.6 nM and 3.9 nM, respectively, but is relatively weak in inhibiting HDAC4 and HDAC6 with IC50 25 nM and 790 nM, respectively. Romidepsin is 17-23 times weaker than redFK in inhibiting these HDACs with IC50 of 36 nM, 47 nM, 510 nM, and 14 μM, respectively. Romidepsin treatment in HeLa cells induces histone acetylation and p21 expression with EC50 of 3.0 nM, more strongly than redFK with EC50 of 11 nM due to the instability of redFK. [1]In addition to G2/M arrest, Romidepsin treatment causes cyclin D1 downregulation and a p53-independent p21 induction, leading to inhibition of CDK and dephosphorylation of Rb resulting in growth arrest in the early G1 phase. [2] Romidepsin is 100 times more potent than TSA and 1,000,000 times more potent than butyrate in inhibiting the proliferation of the A549 cells. [3] Romidepsin inhibits the growth of U-937, K562, and CCRF-CEM cells with IC50 of 5.92 nM, 8.36 nM, and 6.95 nM, respectively. [5] Romidepsin promotes apoptosis in chronic lymphocytic leukemia (CLL) cells at a concentration corresponding to that at which H3 and H4 acetylation and HDAC inhibition occurs, selectively involving activation of caspase 8 and effector caspase 3, as well as down-regulation of c-FLIP protein. [6] In 11 of 13 (85%) renal cell carcinoma cell lines and in 16 of 37 (43%) other cancer cell lines, Romidepsin treatment up-regulates tumor death receptors, and potentiates natural killer (NK)-mediated tumor killing. [7] Romidepsin exhibits concentration-dependent cytotoxicity against a panel of mantle cell lymphoma (MCL) cell lines. [9] | |||||
| In vivo | Romidepsin treatment potently inhibits the neovascularization of chick embryo and that of adult mice in the Matrigel plug assay. [4]Administration of Romidepsin at 0.1-1 mg/kg twice a week significantly prolongs the survival of mice bearing U-937 lymphoma, with median survival times of 30.5 (0.56 mg/kg) and 33 days (0.32 mg/kg), respectively (vs. 20 days in control mice). [5] | |||||
| Features | More effective than other classical HDAC inhibitors such as TSA, TPX, and butyrate. | |||||
Protocol(Only for Reference)
Kinase Assay:
| HDAC-inhibitory activity | For the enzyme assay, 10 μL of [3H]acetyl-labeled histones (25,000 cpm/10 μg) are added to 90 μL of the HDAC enzyme fraction extracted from 293T cells overexpressing HDAC1 or HDAC2 in the presence of increasing concentrations of Romidepsin, and the mixture is incubated at 37 °C for 15 minutes. The enzyme reaction is linear for at least 1 hour. The reaction is stopped by the addition of 10 μL of concentrated HCl. The released [3H]acetic acid is extracted with 1 mL of ethylacetate, and 0.9 mL of the solvent layer is taken into 5 mL of aqueous counting scintillant II solution for determination of radioactivity. The IC50 values are determined from at least three independent dose-response curves. |
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Cell Assay:
| Cell lines | HL60, Jurkat, A549, and MCF-7 |
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| Concentrations | Dissolved in DMSO, final concentrations ~10 μM |
| Incubation Time | 72 hours |
| Method | Cells are exposed to various concentrations of Romidepsin for 72 hours in 96-well plates. 20 μL of 5 mg/mL MTT solution in PBS is added to each well for 4 hours. After removal of the medium, 170 μL of DMSO is added to each well to dissolve the formazan crystals. The absorbance at 540 nm is determined. In addition, cells are incubated with trypan blue, and the numbers of blue (dead) cells and transparent (live) cells are counted in a hemocytometer. For cell cycle analysis, cells are incubated for 30 minutes in propidium iodide staining solution containing 0.05 mg/mL propidium iodide, 1 mM EDTA, 0.1% Triton X-100, and 1 mg/mL RNase A in PBS. The suspension is then passed through a nylon mesh filter and analyzed on a Becton Dickinson FACScan. |
Animal Study:
| Animal Models | Male scid mice inoculated i.p. with U-937 cells |
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| Dosages | ~1 mg/kg once or twice a week |
| Administration | Treated i.p. |
| Solubility | 1% DMSO/30% polyethylene glycol/1% Tween 80, 18 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01638533 | Recruiting | Adult Nasal Type Extranodal NK/T-cell Lymphoma|Anaplastic Large Cell Lymphoma|Angioimmunoblastic T-cell Lymphoma|Cutaneous B-cell Non-Hodgkin Lymphoma|Extranodal Marginal Zone B-cell Lymphoma of Mucos | National Cancer Institute (NCI) | 2012-06 | Phase 1 |
| NCT01590732 | Recruiting | Lymphoma | M.D. Anderson Cancer Center|Celgene Corporation | 2012-10 | Phase 1 |
| NCT01738594 | Recruiting | Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma|Recurrent Mycosis Fungoides/Sezary Syndrome|Stage I Cutaneous T-cell Non-Hodgkin Lymphoma|Stage IA Mycosis Fungoides/Sezary Syndrome|Stage IB Mycosis Fu | Northwestern University|Onyx Pharmaceuticals | 2013-01 | Phase 1 |
| NCT01897012 | Recruiting | B-cell Chronic Lymphocytic Leukemia|Cutaneous B-cell Non-Hodgkin Lymphoma|Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue|Intraocular Lymphoma|Nodal Marginal Zone B-cell | National Cancer Institute (NCI) | 2013-07 | Phase 1 |
| NCT01938833 | Not yet recruiting | HER2-negative Breast Cancer|Inflammatory Breast Cancer|Male Breast Cancer|Recurrent Breast Cancer|Stage IV Breast Cancer | Thomas Jefferson University|Celgene Corporation | 2013-11 | Phase 1|Phase 2 |
Chemical Information
Download Romidepsin (FK228, Depsipeptide) SDF
| Molecular Weight (MW) | 540.7 |
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| Formula | C24H36N4O6S2 |
| CAS No. | 128517-07-7 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 10 mg/mL (18 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 1% DMSO/30% polyethylene glycol/1% Tween 80, | 18 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | Cyclo[(2Z)-2-amino-2-butenoyl-L-valyl-(3S,4E)-3-hydroxy-7-mercapto-4-heptenoyl-D-valyl-D-cysteinyl], cyclic (3→5)-disulfide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.5407 | 5.407 | - | - |
Product Citations (5)
Increasing Tip60 HAT levels rescues axonal transport defects and associated behavioral phenotypes in a Drosophila Alzheimer’s disease model. [Johnson AA, et al. J Neurosci 2013;33(17):7535-47]
Overcoming inherent resistance to histone deacetylase inhibitors in multiple myeloma cells by targeting pathways integral to the actin cytoskeleton. [Mithraprabhu S Cell Death Dis 2014;5:e1134]
Expression of leukemia-associated fusion proteins increases sensitivity to histone deacetylase inhibitor-induced DNA damage and apoptosis. [Petruccelli LA, et al. Mol Cancer Ther 2013;12(8):1591-604]
