Panobinostat (LBH589)
目录号：S1030 别名： NVP-LBH589
Molecular Weight(MW): 349.43
Panobinostat (LBH589)是一种新型的，广谱HDAC抑制剂，无细胞试验中IC50为5 nM。Phase 3。
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客户使用该产品的12个实验数据：
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(G) A375 parental and BRAFi-resistant ex vivo clones were treated with a panel of HDACi (1 μM vorinostat, 0.5 μM belinostat, and 6 nM panobinostat) in single treatment or in combination with 1 μM vemurafenib in a long-term colony formation assay.
Cell, 2018, 173(6):1413-1425. Panobinostat (LBH589) purchased from Selleck.
LSD1 and HDAC inhibitors exhibit synergistic growth inhibition. Cells were simultaneously treated with pargyline or HDAC inhibitors for 48 h.
Breast Cancer Res Treat 2012 131, 777-789. Panobinostat (LBH589) purchased from Selleck.
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Using CRISPR-Cas9 technology, ERα was silenced at the genomic level in ECC1 cells. Ishikawa, parental ECC1 cells and individual ESR1 KO ECC1 clones were treated with 20 nM LBH589 for 24 hr. Expression of ERα, PR, FOXO1, and Myc were evaluated by Western blotting. β-actin serves as a loading control.
PLoS One, 2016, 11(2):e0148912.. Panobinostat (LBH589) purchased from Selleck.
HDACIs That Simultaneously Inhibit HDACs 1 and 6 Showed Greater Antileukemic Activities than HDACIs that Don’t at Cmax Concentrations. THP-1 cells were treated with LBH-589, PXD101, SAHA, VPA, MS-275 and MGCD0103 at Cmax concentrations for 3 h and 24 h, respectively. The cells post 3 h treatments were washed three times with complete medium and divided into two halves. One half of the cells was resuspended in complete media and cultured for up to 24 h to determine the effects of the 3 h treatments on cell proliferation and apoptosis. The other half of the cells was used to prepare whole cell lysates. Whole cell lysates from the 3 h and 24 h treatments were extracted and subjected to Western blots probed by anti-ac-tubulin or –b-actin antibody (panels A&B), or subjected to HDAC1 enzymatic assays post IP as described in the Materials and Methods (Panels C&D). The effects of the 3 h and 24 h HDACI treatments on cell proliferation, as reflected by percent decrease of live cells relative to untreated cells (panel E), and apoptosis (panel F) were determined by flow cytometry analysis as described in the Materials and Methods.
PLoS One 2011 6, e17138. Panobinostat (LBH589) purchased from Selleck.
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Induction of DNA Damage and Bim Is Critical for HDACI-Induced Apoptosis in Pediatric AML Cells. THP-1 cells were treated with the HDACIs at Cmax concentrations for 3 (panel A) and 24 h (panel B), respectively. Whole cell lysates were extracted and subjected to Western blots probed by anti-p21, -c-Myc, -cH2AX, -Bim, or -b-actin antibody.
PLoS One 2011 6, e17138. Panobinostat (LBH589) purchased from Selleck.
Cell death induction by LBH589 as a single agent was detected in control or MTDH knockdown Hec50co cells. After 3 days, cell death was determined by the WST-1 method.
PLoS One 2011 6, e20920. Panobinostat (LBH589) purchased from Selleck.
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Expression of pro-/anti-apoptosis genes. Control or MTDH knockdown Hec50co cells were treated for 24 hours with vehicle control, 20 nM LBH589, 25 ng/ml TRAIL or LBH589 and TRAIL at the concentrations noted. Lysates were collected. Expression of DR4, DR5, and apoptosis related caspase-3, caspase-8, PARP-1, BID, FLIP, XIAP, Bim, MCL-1 and BCL-XL was analyzed by Western blotting.
PLoS One 2011 6, e20920. Panobinostat (LBH589) purchased from Selleck.
p53(+/+) and (/) HCT116 cells were treated with TSA (1–5 lM),LBH589 (2–5 lM), valproate (2.5–5 mM), MS-275 (20 lM) and sodium butyrate (2 mM). TAp63 expression was compared in both cell lines after 24 h of treatment. Consistent with the above data, all HDAC inhibitors failed to induce significant levels of TAp63 in p53(/) HCT116 cells.
Biochem Bioph Res Co 2009 391, 1748-1751. Panobinostat (LBH589) purchased from Selleck.
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Effect of panobinostat on the viability of cervical cancer cells. HeLa (A) and SiHa (B) cells were treated with increasing concentrations of panobinostat for 24, 48 and 72 h. Cell viability was determined by MTT assay. The results are presented as percentage; calculated from the reduction in cell viability at a given concentration of drug compared to the untreated control (untreated control being 100%). The IC5072h values were calculated from sigmoidal dose-response curves generated in Prism 5.0 (GraphPad). (C) Cytotoxic effects of panobinostat on HeLa and SiHa cells measured at 72 h and expressed as% cell death. Each value is the mean ± SD of three independent experiments performed in triplicates.
Biomed Pharmacother, 2016, 84:1393-1405. Panobinostat (LBH589) purchased from Selleck.
Western blot analysis of Acetyl-H3 and H3. 0-10μM Panobinostat was added.
Dr.Zhang of Tianjin Medical University. Panobinostat (LBH589) purchased from Selleck.
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HDAC inhibitors induce p63a expression (A) HCT116 cells were treated with TSA (1 lM), LBH589 (2 lM), valproate (2.5 mM), MS-275 (20 lM) and sodium butyrate(2 mM) for 24 h. Expression of p63 was assessed by Western blotting with the H129 pan-anti-p63 antibody. Although TSA and LBH589 induced p63 efficiently, valproate, MS-275 and sodium butyrate were much less efficient. The lower panel shows the actin loading control. Arrow indicates TAp63. (B) The HDAC inhibitors used in this study are shown, grouped according to their structure and with their HDAC specificity. The efficiency of TAp63 expression is shown in the last column.
Dr. Berna S. Sayan of Leicester University. Panobinostat (LBH589) purchased from Selleck.
U266 and KMS-11 were treated with 20 nM panobinostat for 48 h followed by Western blot analysis. Actin served as a loading control. Nine (U266) and 3 (KMS-11) biologically independent experiments were performed. To determine the expression of PPP3CA mRNA in treated cells for 24 h, we performed relative quantification real-time PCR (n = 6). Four (U266) and 2 (KMS-11) biologically independent experiments were performed.
JCI Insight, 2016, 1(5):e85061. Panobinostat (LBH589) purchased from Selleck.
产品安全说明书
HDAC抑制剂选择性比较
生物活性
| 产品描述 | Panobinostat (LBH589)是一种新型的，广谱HDAC抑制剂，无细胞试验中IC50为5 nM。Phase 3。 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 靶点 |
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| 体外研究 |
LBH589诱导MOLT-4和Reh细胞凋亡，这种作用具有时间和剂量依赖性。而且，LBH589作用于MOLT-4细胞比作用于Reh细胞更有效。LBH589明显阻止MOLT-4 和Reh细胞的生长，处理48小时，具有剂量依赖性。与对照组细胞相比，用LBH589处理的细胞，在细胞周期的G2/M期的细胞数量增多2到3倍。LBH589与组蛋白H3K9和H4K8的乙酰化作用相关，LBH589也降低c-Myc的表达水平，具有剂量依赖性。LBH589也增强p21的表达水平。最低剂量的LBH589（10 nM）处理Reh细胞，最初增强c-Myc的表达水平，之后一直降低c-Myc的表达水平。此外，LBH589促进mRNA水平的促凋亡和DNA修复基因的大量增多。在GADD45G启动子作用下，LBH589诱导乙酰化的组蛋白H3 和H4水平的增多。[1]此外, LBH589抑制非小细胞肺癌细胞系生长，如人类H1299,L55和A549，IC50分别为5,11和30 nM；间皮瘤细胞生长，如人类OK-6和 Ok-5，IC50分别为5和7 nM；及小细胞肺癌细胞系生长，如人类RG-1和LD-T，IC50分别为4和5 nM。[2] |
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| Cell Data |
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| 体内研究 | LBH589作用于患肺癌和间皮瘤动物模型,明显降低肿瘤生长，与对照组相比平均降低62%。LBH589作用于免疫活性鼠和严重联合免疫缺陷鼠效果差不多，说明LBH589抑制肿瘤生长与免疫学无关。LBH589按20 mg/kg剂量腹腔注射，每周持续5天，导致在实验最后肿瘤生长平均下降70%。与相应的对照组肿瘤相比，LBH589作用于H526衍生的肿瘤下降53%，作用于BK-T衍生的肿瘤下降81%, 作用于RG-1衍生的肿瘤下降76%，作用于H69衍生的肿瘤下降 70%。在相同条件和剂量的情况下，LBH589 作用于NSCLC和Meso衍生的移植瘤，导致SCLC衍生的肿瘤中有两种衰退，伴随着BK-T衍生的平均肿瘤尺寸从实验开始时的296 mm3降低到实验结束时的116 mm3，RG-1衍生的平均肿瘤尺寸从实验开始时的185mm3降低到实验结束时的86 mm3。[2] |
推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)
| 细胞实验：[1] |
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| 动物实验：[2] |
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溶解度 (25°C)
| 体外 | DMSO | 69 mg/mL (197.46 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| 体内 |
从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 2% DMSO+48% PEG 300+2% Tween 80+ddH2O |
5mg/mL |
* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。
化学数据
| 分子量 | 349.43 |
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| 化学式 | C21H23N3O2 |
| CAS号 | 404950-80-7 |
| 稳定性 | powder |
| in solvent | |
| 别名 | NVP-LBH589 |
计算器
摩尔浓度计算器
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
稀释计算器
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
分子量计算器
通过输入化合物的化学式来计算其分子量：
注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2
摩尔浓度计算器
临床试验信息
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02032810 | Active not recruiting | Melanoma|Skin Cancer | H. Lee Moffitt Cancer Center and Research Institute|Novartis | January 7 2014 | Phase 1 |
| NCT03256045 | Recruiting | Recurrent Plasma Cell Myeloma|Refractory Plasma Cell Myeloma | University of Washington|National Cancer Institute (NCI) | May 31 2018 | Phase 2 |
| NCT01169636 | Completed | Hodgkin''s Lymphoma | M.D. Anderson Cancer Center|Novartis | January 31 2011 | Phase 1|Phase 2 |
| NCT02676323 | Recruiting | Acute Myeloid Leukemia|Myelodysplastic Syndrome | St. Jude Children''s Research Hospital | May 3 2016 | Phase 1 |
| NCT02717455 | Recruiting | Glioma | Pediatric Brain Tumor Consortium | June 28 2016 | Phase 1 |
| NCT02654990 | Recruiting | Multiple Myeloma | Novartis Pharmaceuticals|Novartis | April 27 2016 | Phase 2 |
技术支持
在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。
如果有其他问题，请给我们留言。
常见问题及建议解决方法
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问题 1：
How to reconstitute the compound for in vivo mice study?
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回答：
We recommend the vehicle is 2 % DMSO, 2 % Tween 80, 48%PEG300, 48% water. The compound is first dissolved in DMSO, then add Tween, PEG300, water in sequence.
