产品说明书

Romidepsin

Print
Chemical Structure| 128517-07-7 同义名 : FR 901228;FK 228;US brand name: Istodax.;NSC 630176. depsipeptide;NSC 630176
CAS号 : 128517-07-7
货号 : A380298
分子式 : C24H36N4O6S2
纯度 : 99%+
分子量 : 540.696
MDL号 : MFCD18433404
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(194.19 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+30% PEG 300+5%Tween 80+water 5 mg/mL

生物活性
靶点

  • HDAC2

    HDAC2, IC50:47 nM

  • HDAC1

    HDAC1, IC50:36 nM
描述 The inhibition of class I HDACs increased the acetylation of histone proteins, which affects the tertiary chromatin structure and leads to altered expression of genes involved in cell proliferation, apoptosis, and differentiation. It makes a key role of HDAC inhibition in anti-proliferation of tumor cells. Romidepsin (Istodax, FK228, FR901228, depsipeptide), produced by Chromobacterium violaceum, can inhibit HDAC1 and HDAC2 with IC50 values of 36 nM and 47 nM (measured by HDACs prepared from 293T cell lysate), respectively[1]. The increase of H4 K5, H4 K12, and H3 K9 acetylation can be observed in mononuclear cells from CLL patients when treated with 0.04 - 0.4 μM romidepsin, with no changes in H4K16 acetylation, H3K14 acetylation or H3K9 methylation. Romidepsin can induce cell death through either apoptosis or cell growth arrest. The induction of apoptosis occurs via TNF receptor pathway in CLL cells treated with 0.00038 - 0.38 μM for 4h[2]. Also, an additional G1 and G2-arrest, as well as induction of p21 can be observed with absence or presence of P53 when cells treated with romidepsin on concentration of 10 - 100 ng/ml for 24 hours, suggesting that romidepsin can cause p53-independent cell cycle arrest. Consistent with that, PC3 (p53-null) cells treated with 10 ng/ml romidepsin for 12h shows the increased level of p21 and growth arrest, which also indicates the effects of romidepsin on induction of p21 and growth arrest is p53-independent[3]. Up to now, romidepsin is approved by FDA to the treatment of CTCL and PTCL. It is also in clinical trials as monotherapy or in combination therapy with various anticancer agents in patients with hematologic and solid malignancies, such as pancreatic, breast, non-small cell lung cancer, and thyroid cancers[4].
作用机制 The intramolecular disulfide bond can bind to the zinc ion in the active-site pocket of HDACs after romidepsin reduced to RedFK228 by cellular glutathione[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
11z 3-100 nM Kinase Assay reduces HDAC enzymatic activity (IC50 = 6.5 ± 0.6 nmol/L) 20605144
1765-92 Growth Inhibition Assay IC50=1.77 nM 18566246
402-91 Growth Inhibition Assay IC50=1.26 nM 18566246
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02661178 Healthy Volunteers Phase 1 Completed - United Kingdom ... 展开 >> Hammersmith Medicines Research London, United Kingdom, NW10 7EW 收起 <<
NCT01663571 - Terminated(Study is permanentl... 展开 >>y closed to enrollment .Collection of private identifiable information is complete Analysis of private identifiable information is complete) 收起 << - United States, New York ... 展开 >> NYU Langone Medical Center New York, New York, United States, 10016 收起 <<
NCT03432741 Breast Adenocarcinoma ... 展开 >> Recurrent Breast Carcinoma Recurrent Hodgkin Lymphoma Recurrent Mycosis Fungoides Recurrent Non-Hodgkin Lymphoma Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Refractory Hodgkin Lymphoma Refractory Mycosis Fungoides Refractory Nodal Marginal Zone Lymphoma Refractory Non-Hodgkin Lymphoma Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Stage IV Breast Cancer AJCC v6 and v7 收起 << Phase 1 Recruiting May 1, 2019 United States, Minnesota ... 展开 >> Mayo Clinic Recruiting Rochester, Minnesota, United States, 55905 Contact: Clinical Trials Referral Office    855-776-0015       Principal Investigator: Grzegorz S. Nowakowski 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.85mL

0.37mL

0.18mL

9.25mL

1.85mL

0.92mL

18.49mL

3.70mL

1.85mL
参考文献

[1]Furumai R, Matsuyama A, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res. 2002 Sep 1;62(17):4916-21.

[2]Aron JL, Parthun MR, et al. Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Blood. 2003 Jul 15;102(2):652-8. Epub 2003 Mar 20.

[3]Sandor V, Senderowicz A, et al. P21-dependent g(1)arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228. Br J Cancer. 2000 Sep;83(6):817-25.

[4]Horodeński J, Pawlowski Z, et al. [Atrophia gyrata choroideae et retinae]. Klin Oczna. 1973 Aug;43(8):929-32.

[5]Jain S, Jirau-Serrano X, et al. Preclinical pharmacologic evaluation of pralatrexate and romidepsin confirms potent synergy of the combination in a murine model of human T-cell lymphoma. Clin Cancer Res. 2015 May 1;21(9):2096-106.

[6]Li Z, Chan KK, et al. A subnanogram API LC/MS/MS quantitation method for depsipeptide FR901228 and its preclinical pharmacokinetics. J Pharm Biomed Anal. 2000 Feb;22(1):33-44.