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

目录号：S1142 Purity: 99.92%

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

CAS: 467214-21-7

规格	价格	库存
10mM (1mL in DMSO)	1570	现货
5mg	794.94	现货
25mg	2432.56	现货
更大包装
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产品质控

批次：纯度： 99.92%

99.92

Alvespimycin (17-DMAG) HCl相关产品

相关靶点	HSP40 HSP70 HSP90 HSP105 HSF1	点击展开
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相关化合物库	激酶抑制剂库血管生成相关化合物库 TGF-beta/Smad信号通路库细胞骨架信号通路化合物库抗心血管疾病化合物库	点击展开

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
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
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
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 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 chk1 degradation at 10 uM after 6 hrs by Western blot method	28816449
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
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
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
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
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 assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=1.34μM.	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
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
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
HCT116	Cytotoxicity assay			Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.05μM.	20662534
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
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
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	Function assay			Binding affinity to Hsp90 in human SKBR3 cells, IC50=0.024μM.	19017562
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
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
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
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
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
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
MDA-MB-231	Function assay			Inhibition of Hsp90 in human MDA-MB-231 cells assessed as her2 degradation, IC50=0.0045μM.	18929486
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
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
SKBR3	Function assay			Inhibition of Hsp90 in human SKBR3 cells, IC50=0.024μM.	26844689
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 assessed as inhibition of cell viability after 48 hrs by MTT assay, IC50=0.39μM.	24582477
AGS	Cytotoxicity assay			Cytotoxicity against human AGS cells by MTT assay, IC50=16μM.	18359631
A2058	Cytotoxicity assay			Cytotoxicity against human A2058 cells by MTT assay, IC50=0.0021μM.	18929486
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
激酶实验	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。30^oC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
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考文献
[1] Ge J, et al. J Med Chem, 2006, 49(15), 4606-4615. [2] Lang SA, et al. Mol Cancer Ther, 2007, 6(3), 1123-1132. [3] Rao R, et al. Cancer Biol Ther, 2009, 8(13), 1273-1280. [4] Schwock J, et al. Cancer Res, 2009, 69(11), 4750-4759. [5] Hertlein E, et al. Blood, 2010, 116(1), 45-53. + 展开

参考文献

+ 展开

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)	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 : 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

DMSO : 131 mg/mL ( (200.54 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

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

体内溶解配方批次：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
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
澄清溶液	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O 该配方已经过Selleck实验室实测。如果上述溶解方案不能满足您的需求，可联系Selleck销售提供定制化测试。	5.000mg/ml (7.65mM)	以 1 mL 工作液为例,取50μL100mg/ml的澄清DMSO储备液加到400μLPEG300中,混合均匀使其澄清;向上述体系中加入50μLTween80,混合均匀使其澄清;然后继续加入500μLddH2O定容至1mL。工作液请现配现用!
澄清溶液	5% DMSO 1 95% Corn oil 该配方已经过Selleck实验室实测。如果上述溶解方案不能满足您的需求，可联系Selleck销售提供定制化测试。	0.300mg/ml (0.46mM)	以1 mL工作液为例，取50μL 6mg/ml的澄清DMSO储备液加到950μL玉米油中，混合均匀。工作液请现配现用！

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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Alvespimycin (17-DMAG) HCl

产品质控

Alvespimycin (17-DMAG) HCl相关产品

相关信号通路图

细胞实验数据示例

生物活性

化学信息&溶解度

实验计算

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