Belinostat

别名: PXD101,NSC726630, PX-105684 中文名称：贝利司他

目录号：S1085 Purity: 99.74%

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

规格	价格	库存
10mM (1mL in DMSO)	RMB 1317.13	现货
10mg	RMB 981.69	现货
50mg	RMB 3030.32	现货
100mg	RMB 4653.78	现货
200mg	RMB 7950.07	现货
1g	RMB 12039.3	现货
更大包装有超大折扣
400-668-6834 info@selleck.cn

客户使用Selleck的Belinostat发表文献90篇

产品质控

批次：纯度： 99.74%

99.74

Belinostat相关产品

相关靶点	HDAC1 HDAC2 HDAC3 HDAC4 HDAC5 HDAC6 HDAC7 HDAC8 HDAC9 HDAC10 HDAC11 HD1 HD2	点击展开
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相关化合物库	激酶抑制剂库 FDA药物库天然产物库已知活性药物库-I 生物活性库Ⅱ	点击展开

HDAC抑制剂选择性比较

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

HDAC ^[1]
(Cell-free assay)

27 nM

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
激酶实验	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30^oC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−80^oC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30^oC温育45分钟。p300蛋白和 20 μL 50% Ni-琼脂糖在4^oC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 37^oC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。37^oC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		24155971
	Growth inhibition assay	Cell viability IC50		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
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-01-11)
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
NCT02680795	Completed	Solid Tumors\|Hematological Malignancies	Acrotech Biopharma Inc.\|Axis Clinicals Limited	April 27 2016	Phase 1

参考文献
[1] Plumb JA, et al. Mol Cancer Ther, 2003, 2(8), 721-728. [2] Buckley MT, et al. J Transl Med, 2007, 5:49. [3] Qian X, et al. Mol Cancer Ther, 2006, 5(8), 2086-2095. [4] Chowdhury S, et al. J Biol Chem, 2011, 286(35), 30937-30948. [5] Duan J, et al. Mol Cancer Ther, 2007, 6(1), 37-50. + 展开

参考文献

+ 展开

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)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

体外溶解度
批次：

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

体内溶解度
批次：

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

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

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）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

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.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
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C6=C5/X	C6:	LOG(C6):
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C8=C7/X	C8:	LOG(C8):