Panobinostat

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Chemical Structure| 404950-80-7 同义名 : LBH589;NVP-LBH589
CAS号 : 404950-80-7
货号 : A165763
分子式 : C21H23N3O2
纯度 : 98%
分子量 : 349.43
MDL号 : -
存储条件：

Pure form Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(300.49 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：

IP 2% DMSO+2% Tween80+30% PEG300+water 9 mg/mL clear

PO 0.5% CMC-Na 50 mg/mL suspension

生物活性
靶点

  • HDAC

    HDAC (Reh cells), IC50:20 nM

    HDAC (MOLT-4 cells), IC50:5 nM
描述 HDACs (Histone deacetylases) are a group of enzymes that remove acetyl groups and regulate the histone tail, protein-DNA interaction, chromatin conformation, and even transcription. There are 18 mammalian HDACs divided into four classes: class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10), class III (sirtuin family: sirt1-sirt7) and class IV (HDAC 11)[1]. Panobinostat, also called as LBH-589 or NVP-LBH589, is broad-spectrum HDAC inhibitor with hydroxamate-based structure (IC50 value measured by cell-free assay not tested). A maximum effect of 85% apoptosis with 20 nM panobinostat in MOLT-4 cells and 80% apoptosis with 50 nM panobinostat in Reh cells can observed at 72h. Panobinostat can inhibit proliferation and cell-cycle progression in the two ALL cells. IC50 of panobinostat in anti-proliferation of MOLT-4 cells is approximately 5 nM and for Reh cells is approximately 20 nM. Compared with the control cells, panobinostat treatment for 24h (up to 50 nM) caused a 2- to 3-fold increase in the number of cells in the G2/M phase. Like other HDAC pan inhibitors, the hyperacetylation of H3K9 and H4K8, which are the biomarkers for the inhibition of class 1 HDACs, can be observed in MOLT-4 cells treated with panobinostat (10 - 50 nM) for 24h in a dose-dependent manner. Accompanied by that, the induction of p21 and p27 expression, as well as a decrease of c-Myc expression can also be found in the same time with 10 - 20 nM panobinostat. Echoing to the cell-arrest and growth inhibition, the apoptosis and DNA damage response genes, like GADD45A, GADD45B, GADD45G, FANCG, and FOXO3A can be increased robustly in the ALL cells after treatment with 50 nM panobinostat for 24h. These suggest that the growth inhibition effect of panobinostat may due to the apoptosis and DNA damage response caused by HDACs inhibition[2]. Panobinostat in combination with bortezomiband dexamethasone is approved by FDA for the treatment for patients with multiple myeloma who receive prior treatment with bortezomib and an immunomodulatory (IMiD) agent[3].
作用机制 Panobinostat has hydroxamate-based structure, which can chelate the Zn2+ ion of HDACs[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
769-P 10/25/50 nM Growth Inhibition Assay 48 h inhibits cell growth in a dose dependent manner synergistically with ritonavir 25279191
769-P 50 nM Apoptosis Assay 48 h induces cell apoptosis combined ritonavir 25279191
769-P 25/50 nM Growth Inhibition Assay 48 h inhibits cell growth in a dose dependent manner synergistically with bortezomib 25176354
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
NCT02506959 Plasma Cell Leukemia ... 展开 >> Plasmacytoma Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma 收起 << Phase 2 Recruiting September 14, 2019 United States, Texas ... 展开 >> M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Yago L. Nieto    713-792-8750    ynieto@mdanderson.org    Principal Investigator: Yago L. Nieto 收起 <<
NCT00449761 Leukemia, Myeloid, Chronic Phase 2 Phase 3 Completed - -
NCT01055483 Acute Myeloid Leukemia Phase 1 Completed - France ... 展开 >> Novartis Investigative Site Paris Cedex 4, France, 75181 Novartis Investigative Site Paris, France, 75475 Germany Novartis Investigative Site Dresden, Germany, 01307 Novartis Investigative Site Frankfurt, Germany, 60590 Novartis Investigative Site Hannover, Germany, 30625 Novartis Investigative Site Ulm, Germany, 89081 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.86mL

0.57mL

0.29mL

14.31mL

2.86mL

1.43mL

28.62mL

5.72mL

2.86mL
参考文献

[1]Yoon S, Eom GH, et al. HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam Med J. 2016 Jan;52(1):1-11.

[2]Scuto A, Kirschbaum M, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. Blood. 2008 May 15;111(10):5093-100.

[3]Raedler LA, et al. Farydak (Panobinostat): First HDAC Inhibitor Approved for Patients with Relapsed Multiple Myeloma. Am Health Drug Benefits. 2016 Mar;9(Spec Feature):84-7.

[4]Ocio EM, Vilanova D, et al. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica. 2010 May;95(5):794-803.

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