Belinostat
别名: PXD101,NSC726630, PX-105684 中文名称：贝利司他
Belinostat是一种新型HDAC抑制剂，无细胞试验中IC50为27 nM，对耐Cisplatin的肿瘤具有活性。Belinostat (PXD101) 可诱导自噬。
Belinostat Chemical Structure
CAS: 866323-14-0
产品质控
批次：
纯度：
99.74%
99.74
Belinostat相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| PC9 | Function Assay | 500 nM | 24 h | decreases EGFR expression | 23515752 |
| H460 | Function Assay | 0.5/1/2 μM | 4 h | inhibits the levels of Akt (p-Akt) and EGFR | 23515752 |
| H1650 | Function Assay | 0.5/1/2 μM | 4 h | inhibits the levels of Akt (p-Akt) and EGFR | 23515752 |
| PC9 | Function Assay | 0.5/1/2 μM | 4 h | inhibits the levels of Akt (p-Akt) and EGFR | 23515752 |
| Panc0327 | Apoptosis Assay | 1 μM | 24 h | induces apoptosis | 23475695 |
| Panc1005 | Apoptosis Assay | 1 μM | 24 h | induces apoptosis | 23475695 |
| Panc0403 | Apoptosis Assay | 1 μM | 24 h | induces apoptosis | 23475695 |
| AsPc1 | Function Assay | 1/10 μM | 24 h | induces growth arrested in G2/M | 23475695 |
| MiaPaCa2 | Function Assay | 1/10 μM | 24 h | induces growth arrested in G2/M | 23475695 |
| T3M4 | Growth Inhibition Assay | 0-800 nM | 48 h | inhibits cell proliferation in a dose dependent manner | 22681698 |
| AsPC-1 | Growth Inhibition Assay | 0-800 nM | 48 h | inhibits cell proliferation in a dose dependent manner | 22681698 |
| Panc-1 | Growth Inhibition Assay | 0-800 nM | 48 h | inhibits cell proliferation in a dose dependent manner | 22681698 |
| T3M4 | Apoptosis Assay | 100/500/1000 nM | 48 h | induces dose dependent apoptosis | 22681698 |
| AsPC-1 | Apoptosis Assay | 100/500/1000 nM | 48 h | induces dose dependent apoptosis | 22681698 |
| Panc-1 | Apoptosis Assay | 100/500/1000 nM | 48 h | induces dose dependent apoptosis | 22681698 |
| HCT116 | Function Assay | 0.9 μM | 24 h | down-regulats TS protein levels after 6 h incubation | 17124594 |
| H1650 | Function Assay | 500 nM | 24 h | decreases EGFR expression | 23515752 |
| H460 | Function Assay | 500 nM | 24 h | decreases EGFR expression | 23515752 |
| PANC-1 | Function Assay | 10 μM | 2/4 h | increases intracellular ROS level | 23743198 |
| PANC-1 | Cell Viability Assay | 1/10 μM | 48 h | decreases cell viability in a dose dependent manner | 23743198 |
| PANC-1 | Function Assay | 10 μM | 2/4/6 h | induces AMPK activation | 23743198 |
| HL-60 | Function Assay | 0.2 μM | 24/48/72 h | enhances RA-induced granulocytic differentiation | 25864732 |
| NB4 | Function Assay | 0.2 μM | 24/48/72 h | enhances RA-induced granulocytic differentiation | 25864732 |
| HL-60 | Function Assay | 2 μM | 24/48 h | blocks cell cycle in S phase | 25864732 |
| NB4 | Function Assay | 2 μM | 24/48 h | blocks cell cycle in S phase | 25864732 |
| HL-60 | Cell Viability Assay | 0.2/2 μM | 24/48/72 h | decreases cell viability in both time and dose dependent manner | 25864732 |
| NB4 | Cell Viability Assay | 0.2/2 μM | 24/48/72 h | decreases cell viability in both time and dose dependent manner | 25864732 |
| Huh-luc/neo7 | Function assay | 1 uM | 1 to 3 hrs | Inhibition of HDAC class 1 in human Huh-luc/neo7 cells assessed as histone H3 acetylation at 1 uM after 1 to 3 hrs by Western blotting analysis | 25937017 |
| PC3 | Function assay | 0.3 uM | 48 hrs | Inhibition of HDAC in human PC3 cells assessed as increase in amount of acetylated histone H3 at 0.3 uM after 48 hrs by Western blot analysis | 27344487 |
| HCT116 | Function assay | 0.3 uM | 48 hrs | Inhibition of HDAC in human HCT116 cells assessed as increase in amount of acetylated histone H3 at 0.3 uM after 48 hrs by Western blot analysis | 27344487 |
| AsPc1 | Growth Inhibition Assay | 48 h | EC50=0.3 μM | 23475695 | |
| Panc0327 | Growth Inhibition Assay | 48 h | EC50=0.5 μM | 23475695 | |
| MiaPaCa2 | Growth Inhibition Assay | 48 h | EC50=0.7 μM | 23475695 | |
| BxPc3 | Growth Inhibition Assay | 48 h | EC50=1.0 μM | 23475695 | |
| Panc0403 | Growth Inhibition Assay | 48 h | EC50=1.1 μM | 23475695 | |
| Panc1005 | Growth Inhibition Assay | 48 h | EC50=1.1 μM | 23475695 | |
| PL45 | Growth Inhibition Assay | 48 h | EC50=20.8 μM | 23475695 | |
| Panc0203 | Growth Inhibition Assay | 48 h | EC50=22.2 μM | 23475695 | |
| HBL-2 | Growth Inhibition Assay | 24 h | IC50=0.4 μM | 20068080 | |
| Jeko-1 | Growth Inhibition Assay | 24 h | IC50=0.2 μM | 20068080 | |
| Granta-519 | Growth Inhibition Assay | 24 h | IC50=56.3 μM | 20068080 | |
| HCT116 | Growth Inhibition Assay | 48 h | EC50=0.28 μM | 17124594 | |
| HCC4006 | Growth Inhibition Assay | 72 h | IC50=0.46 μM | 23515752 | |
| HCC2935 | Growth Inhibition Assay | 72 h | IC50=0.97 μM | 23515752 | |
| HCC827 | Growth Inhibition Assay | 72 h | IC50=0.29 μM | 23515752 | |
| HCC2279 | Growth Inhibition Assay | 72 h | IC50=0.4 μM | 23515752 | |
| PC9 | Growth Inhibition Assay | 72 h | IC50=0.29 μM | 23515752 | |
| H820 | Growth Inhibition Assay | 72 h | IC50=0.4 μM | 23515752 | |
| H1650 | Growth Inhibition Assay | 72 h | IC50=0.88 μM | 23515752 | |
| H1975 | Growth Inhibition Assay | 72 h | IC50=0.68 μM | 23515752 | |
| H520 | Growth Inhibition Assay | 72 h | IC50=0.75 μM | 23515752 | |
| H1299 | Growth Inhibition Assay | 72 h | IC50=1.2 μM | 23515752 | |
| H460 | Growth Inhibition Assay | 72 h | IC50=0.86 μM | 23515752 | |
| H1666 | Growth Inhibition Assay | 72 h | IC50>10 μM | 23515752 | |
| RAW264.7 | Anti-inflammatory assay | 1 hr | Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of IL6 production pre-incubated for 1 hr before LPS stimulation for 24 hrs by ELISA method, IC50 = 0.000059 μM. | 25113875 | |
| HeLa | Function assay | 30 mins | Inhibition of HDAC in human HeLa cells nuclear extracts incubated for 30 mins by fluorescent assay, IC50 = 0.0264 μM. | 25113875 | |
| MDA-MB-231 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.062 μM. | 29456804 | |
| Jurkat | Antiproliferative assay | 48 hrs | Antiproliferative activity against human Jurkat cells after 48 hrs by MTT assay, IC50 = 0.07 μM. | 29533873 | |
| A549 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A549 cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.077 μM. | 29456804 | |
| HeLa | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HeLa cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.087 μM. | 29456804 | |
| MCF7 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human MCF7 cells after 72 hrs by resazurin dye based fluorescence assay, IC50 = 0.096 μM. | 29456804 | |
| HEL | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HEL cells after 48 hrs by MTT assay, IC50 = 0.1 μM. | 29533873 | |
| Huh7 | Antiviral assay | 3 days | Antiviral activity against HCV genotype 1b infected in human Huh7 cells after 3 days by luciferase reporter gene assay, EC50 = 0.12 μM. | 25490700 | |
| HCT116 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HCT116 cells after 48 hrs by SRB assay, GI50 = 0.13 μM. | 27344487 | |
| MOLT4 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human MOLT4 cells after 48 hrs by MTT assay, IC50 = 0.14 μM. | 29533873 | |
| SK-N-BE(2) | Antiproliferative assay | 48 hrs | Antiproliferative activity against human SK-N-BE(2) cells after 48 hrs by MTT assay, IC50 = 0.31 μM. | 29533873 | |
| PC3 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human PC3 cells after 48 hrs by SRB assay, GI50 = 0.39 μM. | 27344487 | |
| PC3 | Antiproliferative assay | 96 hrs | Antiproliferative activity against human PC3 cells after 96 hrs by celltiter 96 assay, IC50 = 0.45 μM. | 21634430 | |
| HeLa | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay, IC50 = 0.51 μM. | 29533873 | |
| HCT116 | Antiproliferative assay | 96 hrs | Antiproliferative activity against human HCT116 cells after 96 hrs by celltiter 96 assay, IC50 = 0.6 μM. | 21634430 | |
| A2780 | Antiproliferative assay | 96 hrs | Antiproliferative activity against human A2780 cells after 96 hrs by celltiter 96 assay, IC50 = 0.67 μM. | 21634430 | |
| HuH7 | Cytotoxicity assay | 3 days | Cytotoxicity against human HuH7 cells assessed as inhibition of cell viability after 3 days by CellTiter 96 assay, CC50 = 0.68 μM. | 25490700 | |
| COLO205 | Antiproliferative assay | 96 hrs | Antiproliferative activity against human COLO205 cells after 96 hrs by celltiter 96 assay, IC50 = 0.7 μM. | 21634430 | |
| A549 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human A549 cells after 48 hrs by SRB assay, GI50 = 0.78 μM. | 27344487 | |
| HL60 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human HL60 cells after 48 hrs by SRB assay, GI50 = 1.09 μM. | 27344487 | |
| K562 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human K562 cells after 48 hrs by MTT assay, IC50 = 1.1 μM. | 29533873 | |
| PC3 | Antiproliferative assay | 48 hrs | Antiproliferative activity against human PC3 cells after 48 hrs by MTT assay, IC50 = 1.3 μM. | 29533873 | |
| NFF | Cytotoxicity assay | 72 hrs | Cytotoxicity against human NFF cells after 72 hrs by SRB assay, IC50 = 1.4 μM. | 28241112 | |
| HEK293 | Cytotoxicity assay | 48 hrs | Cytotoxicity against HEK293 cells after 48 hrs by resazurin assay, IC50 = 1.4 μM. | 28241112 | |
| NFF | Cytotoxicity assay | 72 hrs | Cytotoxicity against human NFF cells after 72 hrs by sulforhodamine B assay, IC50 = 1.42 μM. | 30245402 | |
| HEK293 | Cytotoxicity assay | 48 hrs | Cytotoxicity against HEK293 cells after 48 hrs by resazurin dye based assay, IC50 = 1.42 μM. | 30245402 | |
| RAW264.7 | Anti-inflammatory assay | 1 hr | Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of nitric oxide production pre-incubated for 1 hr before LPS stimulation for 24 hrs by Griess reagent based assay, IC50 = 2.2 μM. | 25113875 | |
| RAW264.7 | Anti-inflammatory assay | 1 hr | Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of TNFalpha production pre-incubated for 1 hr before LPS stimulation for 24 hrs by ELISA method, IC50 = 4.7 μM. | 25113875 | |
| RAW264.7 | Anti-inflammatory assay | 1 hr | Anti-inflammatory activity in LPS-stimulated mouse RAW264.7 cells assessed as suppression of PGE2 production pre-incubated for 1 hr before LPS stimulation for 24 hrs by enzyme immunoassay method, IC50 = 8.28 μM. | 25113875 | |
| HEK293 | Function assay | Inhibition of HDAC6 in HEK293 cells, IC50 = 0.015 μM. | 18308563 | ||
| HEK293 | Function assay | Inhibition of HDAC1 in HEK293 cells, IC50 = 0.018 μM. | 18308563 | ||
| HeLa | Function assay | Inhibition of HDAC in human HeLa cells using Fluor de Lys as substrate by fluorescence assay, IC50 = 0.027 μM. | 23639537 | ||
| HeLa | Function assay | Inhibition of HDAC from human HeLa cells, IC50 = 0.028 μM. | 18247554 | ||
| HEK293 | Function assay | Inhibition of HDAC3 in HEK293 cells, IC50 = 0.046 μM. | 18308563 | ||
| HCT116 | Antiproliferative assay | Antiproliferative activity against human HCT116 cells assessed as growth inhibition, IC50 = 0.16 μM. | 21650221 | ||
| HCT116 | Antiproliferative assay | Antiproliferative activity against human HCT116 cells, IC50 = 0.16 μM. | 21742496 | ||
| H1299 | Antiproliferative assay | Antiproliferative activity against human H1299 cells, IC50 = 0.46 μM. | 21650221 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Belinostat是一种新型HDAC抑制剂，无细胞试验中IC50为27 nM，对耐Cisplatin的肿瘤具有活性。Belinostat (PXD101) 可诱导自噬。 | ||
|---|---|---|---|
| 特性 | Belinostat是Topotarget的领先药物，已经进行过多次临床试验。 | ||
| 靶点 |
|
| 体外研究(In Vitro) | ||||
| 体外研究活性 | Belinostat抑制肿瘤细胞生长(包括A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3，及HS852)，IC50为0.2到0.66 μM。Belinostat 作用于A2780/cp70 和2780AD细胞时活性很低, 这两个细胞是抗cisplatin和doxorubicin的A2780细胞衍生的。Belinostat通过PARP分裂和组蛋白H3/H4的乙酰化而诱导细胞凋亡。[1] Belinostat抑制膀胱癌细胞生长，尤其是5637细胞,细胞在G0-G1期积累, 在S期下降，在 G2-M期上升。[2] Belinostat抑制细胞生长的活性不受多重耐药表现型的影响, 但是docetaxel的活性明显受影响。Belinostat 可以增强docetaxel或carboplatin 抑制OVCAR-3和A2780细胞的活性。Belinostat作用于卵巢癌细胞系也增强微管乙酰化作用。[3] 最新研究显示 Belinostat在TGF-β信号依赖机制中激活蛋白激酶A 和降低survivin mRNA。[4] | |||
|---|---|---|---|---|
| 激酶实验 | 组蛋白脱乙酰基酶活性实验 | |||
| 汇合培养，用冷PBS中冲洗2遍，按200×g 转速离心5分钟。 细胞悬浮在2体积的溶解 buffer 中，60 mm Tris buffer (pH 为7.4)包含30%甘油和450 mm NaCl，用干冰冻结，然后30oC水浴溶解，循环3次。细胞碎片按1.2×104g转速离心5分钟, 然后上清液储存于−80oC中。使用 [3H]乙酰 CoA，通过p300的重组蛋白包括次黄嘌呤-氨基喋呤-胸腺嘧啶域乙酰化组蛋白H4肽段 (序列为SGRGKGGKGLGKGGAKRHRK)。100 μg H4 肽段与次黄嘌呤-氨基喋呤-胸腺嘧啶buffer（buffer包含50 mM Tris HCl pH为8.0, 5% 甘油, 50 mM KCl, 和0.1 mM EDTA），1 mM DTT, 1 mM 4-(2-氨乙基) ，苯磺酰基氟化物, 1×蛋白酶抑制剂, 50 μL纯化的p300, 及1.85 m [3H]乙酰 CoA (4.50Ci/mmol)混合，最终体积为300 μL，在30oC温育45分钟。p300蛋白 和 20 μL 50% Ni-琼脂糖在4oC下温育1小时，然后离心分离。上清液上样到2 mL Sephadex G15 柱中。加入1毫升蒸馏水，收集三滴样片，重复加入蒸馏水直到体积为4-5 mL，收集40滴样片。用2 mL 闪烁液稀释3微升样片，在闪烁计数板上计数，用于鉴定包含标记肽段的样片。合并样片，测定1 μL组合样本，用于测定每个肽段的放射性。在150 μL buffer，2 μL 细胞抽提物，和2 μL Belinostat的混合液中进行反应。加入2 μL [3H] 标记的底物开始反应。样本在 37oC下温育45分钟，加入HCl 和乙酸(终浓度分别为0.72和0.12 M)终止反应。释放的[3H]乙酸盐加到750 μL of 乙酸乙酯中, 按1.2×104g转速 离心5分钟。上层 (600 μL) 转移到3 mL闪烁液，然后计数。 | ||||
| 细胞实验 | 细胞系 | A2780, A2780/cp70, 2780AD, HCT116, HT29, WIL, CALU-3, MCF7, PC3，和HS852细胞 | ||
| 浓度 | 0.016到10 μM | |||
| 孵育时间 | 24小时 | |||
| 方法 | 肿瘤细胞系(A2780, A2780/cp70, 2780AD, HCT116, HT29, WIL, CALU-3, MCF7, PC3，和HS852) 按8×104个细胞/25 cm2 瓶接种在5 mL 培养基中，温育48小时。用Belinostat (0.016 到 10 μm)处理细胞24小时。1 mL 胰蛋白酶/EDTA加到培养瓶中。细胞分离后，加入1 mL培养基，细胞再次悬浮。稀释细胞，按0.5-2×103个细胞/皿移到6cm Petri皿中。37oC下温育10到15天。用PBS冲洗细胞，溶于甲醇，用结晶紫染色，计数大于50个细胞的群落。通过IC50值计算敏感度。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-H2AX(Ser139) / KU70 / KU80 / RAD51 / RAD52 / ERCC1 Acetyl Histone H3 / Acetyl Histone H4 / Acetyl tubulin p21 / p27 SOS1 / SOS2 PARP / p-ERK / p-p38 / p38 / p-BRAF / p-MEK / MEK |
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24155971 | |
| Growth inhibition assay | Cell viability IC50 |
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24155971 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | Belinostat按10mg/kg剂量处理A2780和A2780/cp70 移植瘤，明显延迟肿瘤生长，但是对动物体重没有影响。[1] 在鼠膀胱细胞中，Belinostat也诱导p21WAF1, HDAC 核心和细胞通讯基因。[2] Belinostat按100mg/kg剂量单独处理A2780移植瘤，产生抗癌功效，肿瘤抑制率（TGI）达47% ，这种抑制存在剂量依赖性。100 mg/kg Belinostat和40 mg/kg Carboplatin联用可以延迟肿瘤生长，从18.6 天到22.5 天。 [3] Bortezomib和Belinostat联用，明显抑制肿瘤，此外，作用于携带抗Bortezomib UMSCC-11A移植瘤的鼠显示肠胃毒性 。[5] | |
|---|---|---|
| 动物实验 | Animal Models | 右侧腹皮下注射A2780, A2780/cp70和HCT116细胞的CD1 nu/nu鼠 |
| Dosages | ≤40 mg/kg | |
| Administration | 腹腔注射 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT06406465 | Not yet recruiting | Carcinoma Neuroendocrine|Tumor Neuroendocrine|Tumors Neuroendocrine|Neuroendocrine; Carcinoma|Small Cell; Receptors |
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) |
May 15 2024 | Phase 2 |
| NCT04315233 | Recruiting | Metastatic Breast Cancer|Recurrent Ovarian Carcinoma |
University of Utah|Novartis|Acrotech Biopharma |
May 3 2021 | Phase 1 |
| NCT04703920 | Recruiting | Metastatic Breast Cancer|Metastatic Castration-resistant Prostate Cancer|Metastatic Ovarian Carcinoma |
University of Michigan Rogel Cancer Center|Pfizer|Acrotech Biopharma Inc. |
March 4 2021 | Phase 1 |
| NCT03772925 | Active not recruiting | Recurrent Acute Myeloid Leukemia|Recurrent Myelodysplastic Syndrome|Refractory Acute Myeloid Leukemia|Refractory Myelodysplastic Syndrome |
National Cancer Institute (NCI) |
June 20 2019 | Phase 1 |
化学信息&溶解度
| 分子量 | 318.35 | 分子式 | C15H14N2O4S |
| CAS号 | 866323-14-0 | SDF | Download Belinostat SDF |
| Smiles | C1=CC=C(C=C1)NS(=O)(=O)C2=CC=CC(=C2)C=CC(=O)NO | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 64 mg/mL ( (201.03 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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常见问题及建议解决方法
问题 1:
Could you please give some suggestions for the use of Belinostat in vivo (i.p. injection)?
回答：
For I.P. injection, S1085 Belinostat (PXD101) can be dissolved in 2% DMSO+30% PEG 300+ddH2O at 10 mg/ml clearly. When preparing the solution, please dissolve the compound in DMSO clearly first. Then add PEG, after they mixed well, then dilute with water. Hope this information is useful to you.
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