Alvespimycin (17-DMAG) HCl

别名: NSC 707545,BMS 826476 HCl,KOS 1022 中文名称:阿螺旋霉素盐酸盐

Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl是一种有效的HSP90抑制剂,无细胞试验中IC50为62 nM。 Phase 2。

Alvespimycin (17-DMAG) HCl Chemical Structure

Alvespimycin (17-DMAG) HCl Chemical Structure

CAS: 467214-21-7

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 2351.34 现货
5mg RMB 794.94 现货
25mg RMB 2432.56 现货
更大包装

400-668-6834

info@selleck.cn

免费分装
免费预溶

客户使用Selleck的Alvespimycin (17-DMAG) HCl发表文献66

产品质控

批次: 纯度: 99.92%
99.81

Alvespimycin (17-DMAG) HCl相关产品

相关信号通路图

HSP (HSP90)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
NCI-H526 Function assay 1 uM 96 hrs Inhibition of HSP90-mediated proliferation of human NCI-H526 cells at 1 uM after 96 hrs by sulforhodamine B assay 17603540
NCI-H526 Function assay 1 uM 24 hrs Binding affinity to HSP90 in human NCI-H526 cells at 1 uM after 24 hrs by fluorescence polarization assay 17603540
LN229-Lux Function assay 2.5 to 10 uM 1 hr Inhibition of luciferase activity in human LN229-Lux cells at 2.5 to 10 uM incubated for 1 hr under normoxia followed by 24 hrs under hypoxia by reporter gene assay 22746274
HeLa Function assay 10 uM 6 hrs Inhibition of HSP90 in human HeLa cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method 28816449
HeLa Function assay 10 uM 6 hrs Inhibition of HSP90 in human HeLa cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method 28816449
HeLa Function assay 10 uM 6 hrs Inhibition of HSP90 in human HeLa cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method 28816449
PC3 Function assay 10 uM 6 hrs Inhibition of HSP90 in human PC3 cells assessed as induction of chk1 degradation at 10 uM after 6 hrs by Western blot method 28816449
PC3 Function assay 10 uM 6 hrs Inhibition of HSP90 in human PC3 cells assessed as induction of Akt degradation at 10 uM after 6 hrs by Western blot method 28816449
PC3 Function assay 10 uM 6 hrs Inhibition of HSP90 in human PC3 cells assessed as induction of HSP70 protein expression at 10 uM after 6 hrs by Western blot method 28816449
AGS Function assay 24 hrs Viability of human AGS cells under normoxic conditions after 24 hrs by MTT assay, IC50=16μM. 17583950
Hep3B Function assay 16 hrs Inhibition of HIF1 activation in human Hep3B cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay, IC50=0.061μM. 17583950
AGS Function assay 16 hrs Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay, IC50=0.036μM. 17583950
HuH7 Antiviral assay 3 days Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days by qRT-PCR analysis, EC50=0.0012μM. 18936191
HuH7 Antiviral assay 3 days Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days selected with 40 nM HCV-796 and 800 nM boceprevir by qRT-PCR analysis, EC50=0.0031μM. 18936191
Hep3B Function assay 30 mins Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis, IC50=0.0572μM. 19072214
Hep3B Function assay 16 hrs Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA, IC50=0.0795μM. 19072214
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells after 72 hrs, IC50=0.057μM. 19231864
SKBR3 Cytotoxicity assay 72 hrs Cytotoxicity against human SKBR3 cells after 72 hrs, IC50=0.058μM. 19231864
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs, IC50=0.071μM. 19231864
SKOV3 Cytotoxicity assay 72 hrs Cytotoxicity against human SKOV3 cells after 72 hrs, IC50=0.122μM. 19231864
SKBR3 Cytotoxicity assay 72 hrs Cytotoxicity against human SKBR3 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol, IC50=0.23μM. 19231864
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol, IC50=0.862μM. 19231864
NCI-H596 Cytotoxicity assay 72 hrs Cytotoxicity against NQ01-deficient human NCI-H596 cells after 72 hrs, IC50=1.1μM. 19231864
MDA468 Cytotoxicity assay 72 hrs Cytotoxicity against NQ01-deficient human MDA468 cells after 72 hrs, IC50=1.6μM. 19231864
SKBR3 Cytotoxicity assay 72 hrs Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay, IC50=0.024μM. 19405528
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by celltiter-glo assay, IC50=0.068μM. 19405528
SKOV3 Cytotoxicity assay 72 hrs Cytotoxicity against human SKOV3 cells after 72 hrs by celltiter-glo assay, IC50=0.22μM. 19405528
MCF7 Cytotoxicity assay 72 hrs Cytotoxicity against human MCF7 cells after 72 hrs by celltiter-glo assay, IC50=0.23μM. 19405528
CCRF-CEM Cytotoxicity assay 72 hrs Cytotoxicity against human CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay, IC50=0.54μM. 19405528
CCRF-CEM Cytotoxicity assay 72 hrs Cytotoxicity against human paclitaxel-resistant CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay, IC50=2.5μM. 19405528
Hep3B Function assay 30 mins Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis, IC50=0.057μM. 20469887
Hep3B Function assay 16 hrs Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA, IC50=0.079μM. 20469887
NCI-H1299 Function assay 24 hrs Inhibition of human HSP90 in human NCI-H1299 cells assessed as Akt degradation after 24 hrs by luminex assay, IC50=0.1μM. 21438541
MCF7 Antiproliferative assay 48 hrs Antiproliferative activity against human MCF7 cells assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=0.39μM. 24582477
HCT116 Antiproliferative assay 48 hrs Antiproliferative activity against human HCT116 cells assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=0.78μM. 24582477
SKBR3 Antiproliferative assay 48 hrs Antiproliferative activity against human SKBR3 cells assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=1.34μM. 24582477
A231 Antiproliferative assay 48 hrs Antiproliferative activity against human A231 cells after 48 hrs by MTT assay, IC50=0.17μM. 24763261
MCF7 Antiproliferative assay 48 hrs Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=0.8μM. 24763261
HCT116 Antiproliferative assay 48 hrs Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay, IC50=1.21μM. 24763261
SKBR3 Antiproliferative assay 48 hrs Antiproliferative activity against human SKBR3 cells after 48 hrs by MTT assay, IC50=3.11μM. 24763261
NCI-H1299 Function assay 12 hrs Reduction in oxygen consumption rate in human NCI-H1299 cells incubated for 12 hrs 25383915
PC9 Cytotoxicity assay 72 hrs Cytotoxicity against HGF-induced erlotinib-resistant human PC9 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50=0.01μM. 26844689
Ma1 Cytotoxicity assay 72 hrs Cytotoxicity against HGF-induced erlotinib-resistant human Ma1 cells assessed as inhibition of cell growth after 72 hrs by MTT assay, IC50=0.01μM. 26844689
MDA-MB-231 Function assay Inhibition of Hsp90 in human MDA-MB-231 cells assessed as her2 degradation, IC50=0.0045μM. 18929486
A2058 Cytotoxicity assay Cytotoxicity against human A2058 cells by MTT assay, IC50=0.0021μM. 18929486
AGS Cytotoxicity assay Cytotoxicity against human AGS cells by MTT assay, IC50=16μM. 18359631
HeLa Cytotoxicity assay Cytotoxicity against human HeLa cells by MTT assay, IC50=2.06μM. 18359631
HeLa Function assay Inhibition of TNF-alpha-induced NF-kappaB activation in human HeLa cells, IC50=0.15μM. 18359631
AGS Function assay Inhibition of hypoxia-induced HIF1 activation in human AGS cells by reporter gene assay, IC50=0.0036μM. 18359631
SKOV3 Function assay Degradation of Her2 in SKOV3 cells, EC50=0.046μM. 16854066
SKOV3 Function assay Upregulation of Hsp70 in SKOV3 cells, EC50=0.014μM. 16854066
SKBR3 Function assay Degradation of Her2 in SKBR3 cells, EC50=0.008μM. 16854066
SKBR3 Function assay Upregulation of Hsp70 in SKBR3 cells, EC50=0.004μM. 16854066
SKBr3 Cytotoxicity assay Cytotoxicity against SKBr3 cells, IC50=0.024μM. 16165354
MDA-MB-231 Cytotoxicity assay Cytotoxicity against human MDA-MB-231 cells by MTT assay, IC50=0.0058μM. 18929486
A2058 Function assay Inhibition of Hsp90 in human A2058 cells, EC50=0.0079μM. 18929486
MDA-MB-231 Function assay Inhibition of Hsp90 in human MDA-MB-231 cells assessed as Akt degradation, IC50=0.0176μM. 18929486
A2058 Function assay Inhibition of Hsp90 in human A2058 cells assessed as Akt degradation, IC50=0.0243μM. 18929486
SKBR3 Function assay Binding affinity to Hsp90 in human SKBR3 cells, IC50=0.024μM. 19017562
HCT116 Cytotoxicity assay Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.05μM. 20662534
SKBR3 Function assay Inhibition of Hsp90 in human SKBR3 cells, IC50=0.024μM. 26844689
点击查看更多细胞系数据

生物活性

产品描述 Alvespimycin (17-DMAG, NSC 707545, BMS 826476, KOS 1022) HCl是一种有效的HSP90抑制剂,无细胞试验中IC50为62 nM。 Phase 2。
特性 17-DMAG是抗生素Geldanamycin 的合成衍生物,比现有抗生素具有较低的肝毒性,比相似衍生物17-AAG效果和有效性更强。
靶点
HSP90 [1]
(Cell-free assay)
62 nM
体外研究(In Vitro)
体外研究活性

荧光偏振(FP)为基础的竞争性结合实验中,17-DMAG作用于人类 Hsp90比 17-AAG(IC50 为 119 nM)效果高2倍,IC50为 62 nM。17-DMAG作用于过量表达Hsp90“服务蛋白” Her2的SKBR3和 SKOV3细胞,下调Her2,EC50分别为8 nM和 46 nM, 且诱导 Hsp70,EC50分别为 4 nM和 14 nM,结果产生显著的毒性,GI50分别为 29 nM 和32 nM。[1] 17-DMAG和 Vorinostat 联用,通过显著降低cyclin D1和CDK4, 及c-Myc, c-RAF 和AKT水平,协同诱导培养的MCL细胞和原发性 MCL 细胞凋亡。[3]17-AAG 只有效作用于慢性淋巴细胞白血病 (CLL) 细胞的IKKβ,而17-DMAG 处理,有效导致Hsp90 客户蛋白IKKα 和 IKKβ的消耗,导致 NF-κB p50/p65 DNA结合减少,NF-κB 靶基因转录降低,及caspase依赖性凋亡降低。通过靶向作用于NF-κB 家族,17-DMAG作用于CLL细胞而不是正常T细胞或NK细胞,选择性调节毒性,这种作用存在剂量和时间依赖性。[5]

激酶实验 荧光偏振(FP)为基础的竞争性结合实验
实验使用氟化硼亚甲基二吡咯(BODIPY)标记的Geldanamycin类似物 (BODIPY-AG) 作为探针,根据探针与蛋白结合情况,测定荧光偏振。从 HeLa细胞中分离活性人类Hsp90 蛋白 (α + β 亚型)。 BODIPY-AG 溶液在FP 实验 buffer (20 mM HEPES-KOH, pH 7.3, 1.0 mM EDTA, 100 mM KCl, 5.0 mM MgCl2, 0.01% NP-40, 0.1 mg/mL 新鲜牛γ-球蛋白 (BGG), 1.0 mM 新鲜DTT,和蛋白酶抑制剂,溶于)中新鲜制备。通过10 μL每组含 BODIPY-AG 和Hsp90的溶液,与连续稀释的 17-DMAG(在 FP 实验 buffer中新鲜制备)混合,而获得竞争性曲线。终浓度为10 nM BODIPY-AG, 40 或 60 nM Hsp90,不同浓度 17-DMAG (0.10 nM-10 μM), 和 ≤0.25% DMSO 在384孔板中混合。30oC下温育3小时后, 在EnVision 2100多标记酶标仪上测定荧光 各向异性(γEx = 485 nm, γEm = 535 nm) 。从竞争曲线中获得17-DMAG的IC50值。
细胞实验 细胞系 慢性淋巴细胞白血病(CLL)
浓度 溶于DMSO,终浓度为~1 μM
孵育时间 24, 或48小时
方法

使用不同浓度17-DMAG 处理细胞24,或48小时。为了测量毒性, 加如MTT试剂,实验板再温育24小时,然后使用分光光度法测量。通过膜联蛋白 V-异硫氰酸荧光素和碘化丙啶(PI)染色测定凋亡。

实验图片 检测方法 检测指标 实验图片 PMID
Western blot HSP90 / HSP70 p-Akt / Survivin / MMP2 PARP / Cleaved caspase-3 / Cleaved caspase-8 / Cleaved caspase-9 / PUMA p-ALK / ALK / p-Akt / Akt / p-ERK / ERK α-Tax / α-IKKα / α-IKKβ/ α-NEMO / α-TBK1 / α-p65 / α-p50 28915605
Growth inhibition assay Cell proliferation 28915605
体内研究(In Vivo)
体内研究活性

17-DMAG按5 mg/kg 或 25 mg/kg处理,每周三次,显著降低 TMK-1 移植瘤生长,通过显著降低血管面积和增殖肿瘤细胞数。[2]与抑制FAK信号一致,17-DMAG 按 25 mg/kg剂量处理小鼠,每周三次,显著抑制肿瘤生长,及ME180 和SiHa 移植瘤的转移。[4]17-DMAG 按10 mg/kg 剂量处理TCL1-SCID移植鼠模型,处理16天,显著降低白细胞数,且延长寿命。[5]

动物实验 Animal Models 移植TCL1 白血病细胞的SCID小鼠
Dosages 10 mg/kg
Administration 腹腔注射,每周5次
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00780000 Terminated
Breast Cancer
Bristol-Myers Squibb
April 2008 Phase 2
NCT00248521 Unknown status
Unspecified Adult Solid Tumor Protocol Specific
Institute of Cancer Research United Kingdom|National Cancer Institute (NCI)
October 2005 Phase 1

化学信息&溶解度

分子量 653.21 分子式

C32H48N4O8•HCl

CAS号 467214-21-7 SDF Download Alvespimycin (17-DMAG) HCl SDF
Smiles CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C(=C(C1)C2=O)NCCN(C)C)C)OC)OC(=O)N)C)C)O)OC.Cl
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 100 mg/mL ( 153.09 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

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

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,: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: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: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。

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。

操作手册

如果有其他问题,请给我们留言。

* 必填项

请输入您的姓名
请输入您的邮箱地址 请输入一个有效的邮箱地址
请写点东西给我们
Tags: buy Alvespimycin (17-DMAG) HCl | Alvespimycin (17-DMAG) HCl supplier | purchase Alvespimycin (17-DMAG) HCl | Alvespimycin (17-DMAG) HCl cost | Alvespimycin (17-DMAG) HCl manufacturer | order Alvespimycin (17-DMAG) HCl | Alvespimycin (17-DMAG) HCl distributor
在线咨询
联系我们