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1mg |
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2mg |
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5mg |
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25mg |
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Purity: ≥98%
Romidepsin (formerly FK-228, FR-901228, Depsipeptide, NSC-630176; trade name Istodax) is a novel, potent and naturally occuring bicyclic depsipeptide antibiotic isolated from the bacterium Chromobacterium violaceum with potential anticancer activity. In cell-free assays, Romidepsin exhibits a potent inhibitory effect on histone deacetylase (HDAC1/2), with an IC50 of 36 nM and 47 nM, respectively. Following intracellular activation, romidepsin binds to HDAC and inhibits it, changing gene expression and causing cell differentiation, cell cycle arrest, and apoptosis to be induced. In November 2009, the US FDA authorized romidepsin for the treatment of cutaneous T-cell lymphoma (CTCL), and in June 2011, it was also approved for the treatment of other peripheral T-cell lymphomas (PTCLs).
Targets |
HDAC1 ( IC50 = 36 nM ); HDAC2 ( IC50 = 47 nM ); HDAC4 ( IC50 = 510 nM ); HDAC6 ( IC50 = 14000 nM )
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
In the enzyme assay, 90 μL of the HDAC enzyme fraction extracted from 293T cells overexpressing HDAC1 or HDAC2 in the presence of increasing concentrations of Romidepsin is mixed with 10 μL of [3H]acetyl-labeled histones (25,000 cpm/10 μg). The mixture is then incubated at 37 °C for 15 minutes. For a minimum of 60 minutes, the enzyme reaction is linear. The addition of 10 μL of concentrated HCl stops the reaction. For the purpose of determining radioactivity, 0.9 mL of the solvent layer is added to 5 mL of aqueous counting scintillant II solution after the released [3H]acetic acid is extracted with 1 mL of ethylacetate. At least three separate independent dose-response curves are used to calculate the IC50 values.
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Cell Assay |
In 96-well plates, cells are exposed to different doses of romidepsin for a duration of 72 hours. For four hours, 20 μL of a 5 mg/mL MTT solution in PBS is added to each well. To dissolve the formazan crystals, 170 μL of DMSO is added to each well after the medium has been removed. At 540 nm, the absorbance is calculated. Moreover, trypan blue is added to the cells, and the quantity of transparent (living) and blue (dead) cells is counted in a hemocytometer. Cells are incubated in a 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 for 30 minutes in order to perform a cell cycle analysis. The suspension is then examined using a Becton Dickinson FACScan after being run through a nylon mesh filter.
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Animal Protocol |
Male scid mice inoculated i.p. with U-937 cells
~1 mg/kg once or twice a week Treated i.p. |
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References |
[1]. Cancer Res . 2002 Sep 1;62(17):4916-21. [2]. Br J Cancer . 2000 Sep;83(6):817-25. [3]. Mol Cancer Ther . 2002 Sep;1(11):937-41. [4]. Int J Cancer . 2002 Jan 20;97(3):290-6. [5]. Biochem Pharmacol . 2002 Oct 1;64(7):1079-90. [6]. Blood . 2003 Jul 15;102(2):652-8. [7]. Cancer Res . 2006 Jul 15;66(14):7317-25. |
Molecular Formula |
C24H36N4O6S2
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Molecular Weight |
540.7
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Exact Mass |
540.21
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Elemental Analysis |
C, 53.31; H, 6.71; N, 10.36; O, 17.75; S, 11.86
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CAS # |
128517-07-7
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Appearance |
White to off-white solid powder
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SMILES |
C/C=C\1/C(=O)N[C@H](C(=O)O[C@H]\2CC(=O)N[C@@H](C(=O)N[C@H](CSSCC/C=C2)C(=O)N1)C(C)C)C(C)C
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InChi Key |
OHRURASPPZQGQM-GCCNXGTGSA-N
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InChi Code |
InChI=1S/C24H36N4O6S2/c1-6-16-21(30)28-20(14(4)5)24(33)34-15-9-7-8-10-35-36-12-17(22(31)25-16)26-23(32)19(13(2)3)27-18(29)11-15/h6-7,9,13-15,17,19-20H,8,10-12H2,1-5H3,(H,25,31)(H,26,32)(H,27,29)(H,28,30)/b9-7+,16-6-/t15-,17-,19-,20+/m1/s1
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Chemical Name |
(1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone
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Synonyms |
NSC 630176;FK228; FK 228; FK-228; FR901228; FR-901228; FR 901228; NSC-630176; NSC-630176; depsipeptide; US trade name: Istodax.
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8495 mL | 9.2473 mL | 18.4945 mL | |
5 mM | 0.3699 mL | 1.8495 mL | 3.6989 mL | |
10 mM | 0.1849 mL | 0.9247 mL | 1.8495 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03547700 | Active Recruiting |
Drug: Romidepsin Drug: Ixazomib |
Lymphoma, T-Cell, Peripheral | Ryan Wilcox | November 18, 2021 | Phase 1 Phase 2 |
NCT01638533 | Active Recruiting |
Other: Pharmacological Study Drug: Romidepsin |
Glioma Lymphoma |
National Cancer Institute (NCI) |
June 12, 2012 | Phase 1 |
NCT02393794 | Active Recruiting |
Drug: Romidepsin Drug: Cisplatin Drug: Nivolumab |
Breast Cancer Triple-Negative Breast Cancer |
Priyanka Sharma | July 17, 2015 | Phase 1 Phase 2 |
NCT02616965 | Active Recruiting |
Drug: Brentuximab vedotin Drug: Romidepsin |
Cutaneous T-cell Lymphoma (CTCL) |
Fox Chase Cancer Center | February 22, 2017 | Phase 1 |
NCT04747236 | Recruiting | Drug: Romidepsin Drug: Azacytidine |
PTCL | University of Virginia | February 19, 2021 | Phase 2 |
Dose response of FK228 on endothelial cells. Int J Cancer . 2002 Jan 20;97(3):290-6. td> |
Antiangiogenic activity of FK228 in vitro. Int J Cancer . 2002 Jan 20;97(3):290-6. td> |
Effects of FK228 on neovascularization of chick embryo. Int J Cancer . 2002 Jan 20;97(3):290-6. td> |
Bortezomib interacts synergistically with romidepsin and belinostat in MCL cell lines. Clin Cancer Res . 2010 Jan 15;16(2):554-65. td> |
Bortezomib interacts synergistically with romidepsin and belinostat in MCL cell lines. Clin Cancer Res . 2010 Jan 15;16(2):554-65. td> |
Treatment with belinostat but not romidepsin results in increased α-tubulin acetylation, whereas coadministration of bortezomib does not affect this event but blocks proteasomal process of NF-κB components. Clin Cancer Res . 2008 Jan 15;14(2):549-58. td> |
Depsipeptide induction of lysine-specific changes in histone acetylation. Blood . 2003 Jul 15;102(2):652-8. td> |