Panobinostat (LBH589)
(Synonyms: 帕比司他; LBH589; NVP-LBH589) 目录号 : GC12257
Panobinostat (LBH589)是一种强效，且具有口服活性和抗肿瘤活性的广谱组蛋白去乙酰化酶（HDAC）抑制剂，IC50值为5nM。
Cas No.:404950-80-7
Sample solution is provided at 25 µL, 10mM.
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Panobinostat (LBH589) is a potent, orally active, broad-spectrum histone deacetylase (HDAC) inhibitor with antitumor activity, exhibiting an IC50 value of 5nM[1]. Panobinostat induces hyperacetylation of histones and other intracellular proteins, allowing the expression of previously suppressed genes, thereby inhibiting cell proliferation and inducing apoptosis in malignant cells[2]. Panobinostat is commonly used in the treatment and research of diseases such as acute myeloid leukemia (AML), multiple myeloma (MM), Hodgkin's lymphoma (HL), and cutaneous T-cell lymphoma (CTCL)[3].
In vitro, treatment of small cell lung cancer (SCLC) H69 cells with panobinostat (20nM) alone for 60h resulted in >70% cell death, accompanied by an increase in the proportion of sub-G1 phase cells[4]. Treatment of various human and mouse melanoma cell lines (e.g., B16, WM793, and WM983A) with panobinostat (12.5-100nM) for 72h effectively inhibited cell growth, with IC50 values ranging from 25 to 100nM, while showing no effect on the growth of untransformed normal melanocytes[5]. Panobinostat (20nM) treatment of HUT78 and HH cells for 24h significantly induced caspase-3/7 activation, with an EC50 value of approximately 10nM[6].
In vivo, intravenous administration of panobinostat (7.5 or 15mg/kg/day; 5 days/week) for 2 weeks in CB.17 SCID mice bearing HH cell CTCL xenografts induced significant tumor regression (41% and 94%, respectively) and prolonged survival time[6]. Intraperitoneal injection of panobinostat (20mg/kg; 3 times/week) for 7 weeks in female nude mice inoculated with MDA-MB-231 cells significantly suppressed tumor volume growth, upregulated APCL gene expression in tumor xenografts, and downregulated β-catenin expression[7].
References:
[1] SCUTO A, KIRSCHBAUM M, KOWOLIK C, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells[J]. Blood, 2008, 111(10): 5093-5100.
[2] ANNE M, SAMMARTINO D, BARGINEAR M F, et al. Profile of panobinostat and its potential for treatment in solid tumors: an update[J]. OncoTargets and Therapy, 2013, 6: 1613-1624.
[3] PRINCE H M, BISHTON M J, JOHNSTONE R W. Panobinostat (LBH589): a potent pan-deacetylase inhibitor with promising activity against hematologic and solid tumors[J]. Future Oncology, 2009, 5(5): 601-612.
[4] CRISANTI M C, WALLACE A F, KAPOOR V, et al. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer[J]. Molecular Cancer Therapeutics, 2009, 8(8): 2221-2231.
[5] WOODS D M, WOAN K, CHENG F, et al. The antimelanoma activity of the histone deacetylase inhibitor panobinostat (LBH589) is mediated by direct tumor cytotoxicity and increased tumor immunogenicity[J]. Melanoma Research, 2013, 23(5): 341-348.
[6] SHAO W, GROWNEY J D, FENG Y, et al. Activity of deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma models: defining molecular mechanisms of resistance[J]. International Journal of Cancer, 2010, 127(9): 2199-2208.
[7] QIN G, LI Y, XU X D, et al. Panobinostat (LBH589) inhibits Wnt/β-catenin signaling pathway via upregulating APCL expression in breast cancer[J]. Cellular Signalling, 2019, 59: 62-75.
Panobinostat (LBH589)是一种强效，且具有口服活性和抗肿瘤活性的广谱组蛋白去乙酰化酶（HDAC）抑制剂，IC50值为5nM[1]。Panobinostat可使组蛋白和其他细胞内蛋白过度乙酰化，允许表达原本受到抑制的基因，从而抑制细胞增殖和诱导恶性细胞凋亡[2]。Panobinostat通常用于急性髓系白血病 (AML)、多发性骨髓瘤 (MM)、霍奇金淋巴瘤 (HL)和皮肤 T 细胞淋巴瘤（CTCL）等疾病的治疗和研究[3]。
在体外，panobinostat（20nM）单独处理小细胞肺癌（SCLC）H69细胞60h，导致>70%细胞无法存活，并伴随sub-G1期细胞的比例增加[4]。Panobinostat（12.5-100nM）处理多种人和小鼠黑色素瘤细胞系（B16、WM793和WM983A等）72h，能有效抑制细胞生长，IC50值为25-100nM，且对未转化的正常黑色素细胞生长无影响[5]。Panobinostat（20nM）处理HUT78和HH细胞24h，显著诱导了caspase-3/7活化，EC50值约为10nM[6]。
在体内，panobinostat（7.5或15mg/kg/day; 5 days/week）通过静脉注射治疗携带HH细胞 CTCL异种移植瘤的CB.17 SCID小鼠2周，可诱导肿瘤的显著消退（分别为41%和94%），并延长小鼠的生存时间[6]。Panobinostat（20mg/kg; 3 times/week）通过腹腔注射治疗接种了MDA-MB-231细胞的雌性裸鼠7周，能显著抑制肿瘤体积的增长，并上调肿瘤异种移植组织中APCL基因的表达，同时下调β-catenin的表达[7]。
| Cell experiment [1]: | |
Cell lines | B16、WM793 and WM983A (melanoma cell lines) |
Preparation Method | Two human (WM793 and WM983A) and one murine (B16) melanoma cell lines were plated in triplicate and treated for 72h with indicated doses of panobinostat (12.5, 25, 50, and 100nM). An MTS assay was used to determine relative amounts of metabolically active cells. |
Reaction Conditions | 12.5, 25, 50, and 100nM; 72h |
Applications | All treated cell lines displayed significant, dose-dependent impairment in growth, IC50 values ranged from 25 to 100nM. And at the concentrations used, no impairment in the growth of normal melanocytes was observed. |
| Animal experiment [2]: | |
Animal models | HH CTCL xenograft CB.17 SCID mouse model |
Preparation Method | Beginning at 13 days post-tumor implant, HH CTCL tumor-bearing mice were treated with panobinostat at 2 different doses. Mice bearing HH tumors were treated with 2 different doses (7.5mg/kg or 15mg/kg) of panobinostat i.v. daily, 5 days per week, for 2 weeks. |
Dosage form | 7.5, and 15mg/kg/day; 5 days/week; 2 week; i.v. |
Applications | Panobinostat treatment resulted in significant tumor regression of 41% and 94% at 7.5 and 15mg/kg, respectively. Mice treated with panobinostat showed some level of dose- and time-dependent body weight loss, but within the acceptable tolerability margin of -15%. Following treatment cessation, panobinostat-treated animals demonstrated delay of tumor growth and extended time to endpoint (TTE) of 41.8 and 61.6 days with 7.5 and 15mg/kg doses, respectively. |
References: | |
| Cas No. | 404950-80-7 | SDF | |
| 别名 | 帕比司他; LBH589; NVP-LBH589 | ||
| 化学名 | (E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide | ||
| Canonical SMILES | CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)C=CC(=O)NO | ||
| 分子式 | C21H23N3O2 | 分子量 | 349.43 |
| 溶解度 | ≥ 17.47mg/mL in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8618 mL | 14.309 mL | 28.618 mL |
| 5 mM | 572.4 μL | 2.8618 mL | 5.7236 mL |
| 10 mM | 286.2 μL | 1.4309 mL | 2.8618 mL |
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动物数量 | 只 |
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