A8173-5mg | Romidepsin (FK228, depsipeptide) [128517-07-7] Clinisciences

Background

Romidepsin, also known as FK228 or depsipeptide, is potent and selective inhibitor of histone deacetylases (HDACs) which are associated with the regulation of re-expression of silenced tumor suppressor genes. It was the first HDAC inhibitor to manifest anti-tumor activity and originally isolated from a rod-shaped Gram-negative bacterium, Chromobacterium violaceum, found in a Japanese soil sample. Romidepsin exhibits a stronger inhibition towards HDAC1 and HDAC2 enzymes (class I), removing acetyl groups from the lysine residues of N-terminal histone tails and maintaining a more open and transcriptionally active chromatin state, than HDAC4 and HDAC6 enzymes (class II). Besides HDAC inhibition, romidepsin is also able to induce cell cycle arrest, cellular differentiation, apoptosis and alteration of gene expression in adult malignancies.

Reference

Karen M VanderMolen, William McCulloch, Cedric J Pearce and Nicholas H Oberlies. Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. The Journal of Antibiotics 2011: 64, 525-531

Jyoti Panicker, Zhijie Li, Christine McMahon, Caroline Sizer, Kenneth Steadman, Richard Piekarz, Susan E. Bates and Carol J. Thiele. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells. Cell Cycle 2010 9: 9, 1830-1838

Product Citation

1. Amy E Neely, Laura A Blumensaadt, et al. "NUP98 and RAE1 sustain progenitor function through HDAC-dependent chromatin targeting to escape from nucleolar localization." Commun Biol. 2023 Jun 23;6(1):664. PMID: 37353594
2. Rie Hagiwara, Kazunori Kageyama, et al. "Involvement of histone deacetylase 1/2 in adrenocorticotropic hormone synthesis and proliferation of corticotroph tumor AtT-20 cells." Peptides. 2020 Nov 9;136:170441. PMID:33181265
3. Tiffany C. Chang, Margarite D. Matossian, et al. "Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor." bioRxiv. 2019 November 29.
4. Kulpa DA, Talla A, et al. "Differentiation to an effector memory phenotype potentiates HIV-l latency reversal in CD4+ T cells." J Virol. 2019 Oct 2. pii: JVI.00969-19. PMID:31578289
5. Tang Y, Yu W. "SIRT1 and p300/CBP regulate the reversible acetylation of serine-threonine kinase NDR2." Biochem Biophys Res Commun. 2019 Aug 16. pii: S0006-291X(19)31586-4. PMID:31427083
6. Kim SR, Lewis JM, et al. "BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition." Oncotarget. 2018 Jun 26;9(49):29193-29207. PMID:30018745
7. Nakano Y, Kelly MC, et al. "Defects in the Alternative Splicing-Dependent Regulation of REST Cause Deafness." Cell. 2018 Jul 26;174(3):536-548.e21. PMID:29961578
8. Ho CF, Bon CP, et al. "Expression of DHA-Metabolizing Enzyme Alox15 is Regulated by Selective Histone Acetylation in Neuroblastoma Cells." Neurochem Res. 2017 Dec 12. PMID:29235036
9. Tarasenko N, Chekroun-Setti H, et al. "COMPARISON OF THE ANTICANCER PROPERTIES OF A NOVEL VALPROIC ACID PRODRUG TO LEADING HISTONE DEACETYLASE INHIBITORS." J Cell Biochem. 2017 Nov 14. PMID:29135083
10. Bagnall NH, Hines BM, et al."Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina." Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):51-60. PMID:28110187
11. a RC, Popova EY, et al. "Histone Deacetylase 1 Is Essential for Rod Photoreceptor Differentiation by Regulating Acetylation at Histone H3 Lysine 9 and Histone H4 Lysine 12 in the Mouse Retina."J Biol Chem. 2017 Feb 10;292(6):2422-2440. PMID:28028172
12. Li QQ, Hao JJ, et al. "Histone deacetylase inhibitor-induced cell death in bladder cancer is associated with chromatin modification and modifying protein expression: A proteomic approach." Int J Oncol. 2016 Jun;48(6):2591-607. PMID:27082124

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Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	540.7
Cas No.	128517-07-7
Formula	C₂₄H₃₆N₄O₆S₂
Synonyms	Istodax, Antibiotic FR 901228, FK228, FR 901228, FK-228, Romidepsin
Solubility	≥27.04 mg/mL in DMSO; insoluble in H2O; ≥35.27 mg/mL in EtOH with ultrasonic
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
SDF	Download SDF
Canonical SMILES	CC=C1C(=O)NC(C(=O)OC2CC(=O)NC(C(=O)NC(CSSCCC=C2)C(=O)N1)C(C)C)C(C)C
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment:
Cell lines	Human NB cell (SMS-KCNR, SK-N-BE2, SH-SY5Y, SK-N-AS, L A1-15N, SH-SHEP and IMR32 lines)
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Reaction Conditions	72h; IC50 ranged from 1-6.5 ng/mL
Applications	Romidepsin (0.5-30 ng/mL) resulted in a dose-dependent decrease in cell viability of all NB cell lines as measured by the MTT or MTS assay. The romidepsin IC50 ranged from 1-6.5 ng/mL in different NB cell lines. Morphological examination by light microscopy revealed that all of the NB cell lines treated with romidepsin had a dose-dependent decrease in cell number and extensive change in morphology to rounded, denser and non-adherent cells.
Animal experiment:
Animal models	Normal and nude mice
Dosage form	1.0-10 kg/mL; i.v.; the tail injection
Applications	Clolon 38 and Colon 26 were implanted sc and M5076 and Meth A were implanted id in mice on Day 0. When the drug were given beginning on Day 1. romidepsin markedly inhibited the growth of Colon 38 and M5076, but not Colon 26 or Meth A. In addition, when the drug were given beginning on Day 4, or on 7 or 8, romidepsin potently inhibited the growth of Colon 38, M5076 and Meth A, and its activities against M5076 and Meth A were potent than when it was given beginning on Day 1.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Panicker J, Li Z, McMahon C, et al. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells [J]. Cell Cycle, 2010, 9 (9): 1830-1838. [2] Ueda H1, Manda T, Matsumoto S, Mukumoto S, Nishigaki F, Kawamura I, Shimomura K. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice [J]. Antibiot (Tokyo). 1994 Mar; 47 (3): 315-23.

Biological Activity

Description	Romidepsin (FK228, depsipeptide) is a potent and selective inhibitor of class I histone deacetylases (HDACs) with IC50 values of 36, 47, 510 and 14,000 nM for HDAC1, HDAC2, HDAC4 and HDAC6, respectively.
Targets	HDAC1	HDAC2
IC50	36 nM	47 nM