Ganetespib (STA-9090)

Ganetespib (STA-9090)是一种HSP90抑制剂,在OSA 8种细胞中IC50为4 nM,诱导OSA细胞凋亡,而不影响正常的成骨细胞;是STA-1474的活性代谢物。Phase 3。

Ganetespib (STA-9090) Chemical Structure

Ganetespib (STA-9090) Chemical Structure

CAS: 888216-25-9

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1392.3 现货
5mg RMB 1122.03 现货
50mg RMB 7944.3 现货
1g RMB 33554.43 现货
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批次: 纯度: 99.97%
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Ganetespib (STA-9090)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
A1847 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
H2228 Cell Viability Assay 0-1000 nM 72 h IC50=13 nM 23533265
H3122 Cell Viability Assay 0-1000 nM 72 h IC50=10 nM 23533265
K008 Function Assay 250 nM 24 h induces G2 arrest 23418523
K028 Function Assay 250 nM 24 h induces G2 arrest 23418523
K029 Function Assay 250 nM 24 h induces G1 arrest 23418523
M23 Function Assay 250 nM 24 h induces G1 and G2/M arrest 23418523
K033 Function Assay 250 nM 24 h induces a modest increase in G1 population 23418523
K008 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K028 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K029 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
M23 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
K033 Apoptosis Assay 100 nM 72 h significantly induces apoptosis 23418523
OVCAR-8 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
OVCAR-5 Apoptosis Assay 10-100 nM 24/48/72 h induces apoptosis time and dose dependently 23900136
SKOV-3 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
A1847 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
OVCAR-8 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
OVCAR-5 Cell Viability Assay 0-1000 nM 72 h inhibits cell viability dose dependently 23900136
H146  Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
GLC4 Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
H82 Function Assay 30 nM 72 h induces persistent G2/M phase arrest 24166505
MDA-MB-231 Function Assay 100 nM 24 h inhibits the migratory and invasive capacity  24173541
BT-20  Function Assay 100/250 nM 24 h resulted in a dose-dependent destabilization of EGFR, IGF-IR, MET, and CRAF 24173541
MDA-MB-435 Function Assay 100 nM 30 min inhibits accumulation of HIF-1α 24248265
MDA-MB-231 Function Assay 100 nM 30 min inhibits accumulation of HIF-1α 24248265
CAL27 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
Detroit562 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
FUDA Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
SCC25 Cytoxicity Assay 10/50 nM 24 h decreases cell proliferation dose dependently 25205430
HT-29 Function Assay 50nM 24 h induced G0/G1 arrest 25210794
HCT-116 Function Assay 50nM 24 h induced G0/G1 arrest 25210794
MGC-803 Function Assay 0.1-1000 nM 24 h induces G2/M cell-cycle arrest 25590805
MKN-28 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
SGC-7901 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
MGC-803 Cell Viability Assay 0.1-1000 nM 72 h inhibits cell viability dose dependently 25590805
MV411 Apoptosis Assay 30/80/150/250 nM 24/48/72 h induces dose dependant induction of apoptosis 25882550
HL60 Apoptosis Assay 30/80/150/250 nM 24/48/72 h induces dose dependant induction of apoptosis 25882550
NCI-H1975 Growth Inhibition Assay 48 h IC50=16 nM 22144665
NCI-H1975 Growth Inhibition Assay 72 h IC50=8 nM 22144665
K008 Cell Viability Assay IC50=60 nM 23418523
K028 Cell Viability Assay IC50=84 nM 23418523
K029 Cell Viability Assay IC50=46 nM 23418523
M23 Cell Viability Assay IC50=37.5 nM 23418523
K033 Cell Viability Assay IC50=75.5 nM 23418523
RD Growth Inhibition Assay IC50=8 nM 23303741
Rh41 Growth Inhibition Assay IC50=10.4 nM 23303741
Rh18 Growth Inhibition Assay IC50=6.2 nM 23303741
Rh30 Growth Inhibition Assay IC50=5.6 nM 23303741
BT-12 Growth Inhibition Assay IC50=14.3 nM 23303741
CHLA-266 Growth Inhibition Assay IC50=27.1 nM 23303741
TC-71 Growth Inhibition Assay IC50=4.5 nM 23303741
CHLA-9 Growth Inhibition Assay IC50=4.6 nM 23303741
CHLA-10 Growth Inhibition Assay IC50=5.7 nM 23303741
CHLA-258 Growth Inhibition Assay IC50=6.4 nM 23303741
SJ-GBM2 Growth Inhibition Assay IC50=12.9 nM 23303741
NB-1643 Growth Inhibition Assay IC50=7.4 nM 23303741
NB-EBc1 Growth Inhibition Assay IC50=16.8 nM 23303741
CHLA-90 Growth Inhibition Assay IC50=22.3 nM 23303741
CHLA-136 Growth Inhibition Assay IC50=23.2 nM 23303741
NALM-6 Growth Inhibition Assay IC50=11.7 nM 23303741
COG-LL-317 Growth Inhibition Assay IC50=4.4 nM 23303741
RS4;11 Growth Inhibition Assay IC50=13.5 nM 23303741
MOLT-4 Growth Inhibition Assay IC50=10.6 nM 23303741
CCRF-CEM (1) Growth Inhibition Assay IC50=12.5 nM 23303741
CCRF-CEM (2) Growth Inhibition Assay IC50=7.2 nM 23303741
Kasumi-1 Growth Inhibition Assay IC50=5.8 nM 23303741
Karpas-299 Growth Inhibition Assay IC50=9.6 nM 23303741
Ramos-RA1 Growth Inhibition Assay IC50=7.4 nM 23303741
LNCaP Growth Inhibition Assay IC50=8 nM 23152004
VCaP Growth Inhibition Assay IC50=7 nM 23152004
H1355 Growth Inhibition Assay IC50=5 nM 23012248
H157 Growth Inhibition Assay IC50=7 nM 23012248
H460 Growth Inhibition Assay IC50=8 nM 23012248
IA-LM Growth Inhibition Assay IC50=10 nM 23012248
HOP-62 Growth Inhibition Assay IC50=11 nM 23012248
H23 Growth Inhibition Assay IC50=11 nM 23012248
H2030 Growth Inhibition Assay IC50=12 nM 23012248
H441 Growth Inhibition Assay IC50=14 nM 23012248
H2212 Growth Inhibition Assay IC50=17 nM 23012248
SK-LU-1 Growth Inhibition Assay IC50=18 nM 23012248
H2009 Growth Inhibition Assay IC50=19 nM 23012248
H1792 Growth Inhibition Assay IC50=20 nM 23012248
COR-L23 Growth Inhibition Assay IC50=22 nM 23012248
H727 Growth Inhibition Assay IC50=28 nM 23012248
H1734 Growth Inhibition Assay IC50=28 nM 23012248
H358 Growth Inhibition Assay IC50=29 nM 23012248
A549 Growth Inhibition Assay IC50=43 nM 23012248
H2122 Growth Inhibition Assay IC50=53 nM 23012248
Calu-1 Growth Inhibition Assay IC50=58 nM 23012248
Calu-6 Growth Inhibition Assay IC50=64 nM 23012248
AC3 Growth Inhibition Assay IC50=25.9 nM 24166505
H1173 Growth Inhibition Assay IC50=12.62 nM 24166505
H792 Growth Inhibition Assay IC50=45.07 nM 24166505
H620 Growth Inhibition Assay IC50=32.67 nM 24166505
N592 Growth Inhibition Assay IC50=14.12 nM 24166505
H526 Growth Inhibition Assay IC50=21.64 nM 24166505
H187 Growth Inhibition Assay IC50=24.99 nM 24166505
H146 Growth Inhibition Assay IC50=28.51 nM 24166505
H128 Growth Inhibition Assay IC50=69.55 nM 24166505
H69 Growth Inhibition Assay IC50=83.36 nM 24166505
GLC4 Growth Inhibition Assay IC50=20.47 nM 24166505
H82 Growth Inhibition Assay IC50=30.27 nM 24166505
HCC2998 Growth Inhibition Assay IC50=128 nM 24682747
SK-CO-1 Growth Inhibition Assay IC50=81 nM 24682747
LS-123 Growth Inhibition Assay IC50=73 nM 24682747
SNU-C2B Growth Inhibition Assay IC50=45 nM 24682747
LS-1034 Growth Inhibition Assay IC50=31 nM 24682747
LoVo Growth Inhibition Assay IC50=22 nM 24682747
COLO-678 Growth Inhibition Assay IC50=21 nM 24682747
NCI-H747 Growth Inhibition Assay IC50=17 nM 24682747
COLO-205 Growth Inhibition Assay IC50=14 nM 24682747
HCT 116 Growth Inhibition Assay IC50=14 nM 24682747
HuTu-80 Growth Inhibition Assay IC50=13 nM 24682747
HCT-15 Growth Inhibition Assay IC50=8 nM 24682747
SW620 Growth Inhibition Assay IC50=8 nM 24682747
LS-411 N Growth Inhibition Assay IC50=5 nM 24682747
RKO Growth Inhibition Assay IC50=4 nM 24682747
SW780 Growth Inhibition Assay IC50=3451 nM 24784839
RT4 Growth Inhibition Assay IC50=1733 nM 24784839
TCCSUP Growth Inhibition Assay IC50=142 nM 24784839
MGH-U3 Growth Inhibition Assay IC50=53 nM 24784839
HT-1197 Growth Inhibition Assay IC50=53 nM 24784839
5637 Growth Inhibition Assay IC50=44 nM 24784839
35612 Growth Inhibition Assay IC50=38 nM 24784839
KU-19-19 Growth Inhibition Assay IC50=36 nM 24784839
LB831-BLC Growth Inhibition Assay IC50=34 nM 24784839
UM-UC3 Growth Inhibition Assay IC50=33 nM 24784839
647-V Growth Inhibition Assay IC50=27 nM 24784839
HT-1376 Growth Inhibition Assay IC50=21 nM 24784839
J82 Growth Inhibition Assay IC50=18 nM 24784839
BFTC Growth Inhibition Assay IC50=17 nM 24784839
SCaBER Growth Inhibition Assay IC50=10 nM 24784839
639-V Growth Inhibition Assay IC50=10 nM 24784839
RT112 Growth Inhibition Assay IC50=9 nM 24784839
T24 Growth Inhibition Assay IC50=7 nM 24784839
SW-1710 Growth Inhibition Assay IC50=6 nM 24784839
DSH1 Growth Inhibition Assay IC50=6 nM 24784839
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
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生物活性

产品描述 Ganetespib (STA-9090)是一种HSP90抑制剂,在OSA 8种细胞中IC50为4 nM,诱导OSA细胞凋亡,而不影响正常的成骨细胞;是STA-1474的活性代谢物。Phase 3。
靶点
HSP90 [1]
(OSA 8 cells)
4 nM
体外研究(In Vitro)
体外研究活性 Ganetespib对恶性肥大细胞系的50%抑制浓度(IC50)比对17-AAG低10-15倍,表明三唑酮类HSP90抑制剂可能比格尔德霉素类抑制剂具有更高的效能。[1] Ganetespib抑制MG63细胞系,IC50为43 nM。[1] Ganetespib结合于Hsp90的N末端ATP结合域,通过引起多重致瘤性Hsp90受体蛋白,包括HER2/neu,突变型EGFR,Akt,c-Kit,IGF-1R,PDGFRα,Jak1,Jak2,STAT3,STAT5,HIF-1α,CDC2和c-Met 以及Wilms' tumor 1的降解,成为一种有效的Hsp90的抑制剂。[2] Ganetespib,在纳摩尔级低浓度下,有效阻滞细胞增殖,并诱导广泛的人肿瘤细胞系凋亡,并且对许多受体酪氨酸激酶抑制剂-和tanespimycin-耐受的细胞系也具有作用。Ganetespib在一系列固体和血液肿瘤细胞系,包括那些对小分子酪氨酸激酶抑制剂耐受的表达突变激酶的细胞系,都表现出有效的细胞毒性。[3] Ganetespib治疗快速引起已知的Hsp90受体蛋白降解,表现出高于ansamycin抑制剂17-AAG的效能,并且在较短的暴露时间下也具有持续的活性。[3]在另一个研究中,Ganetespib诱导恶性犬肥大细胞系凋亡。Ganetespib在非常低的浓度下,有效作用于C2和BR犬恶性肥大细胞,IC50分别为19和4 nM,而17-AAG抑制C2和BR犬恶性肥大细胞的IC50分别为958和44 nM。[4]100 nM Ganetespib处理24小时后,所有处理过的细胞系,包括C2和BMCMCs细胞中WT和突变型Kit的表达被下调。然而,Ganetespib处理后不影响PI3K或HSP90的表达。[4]
细胞实验 细胞系 OSA细胞
浓度 0.001-1μM
孵育时间 5天
方法 将1.5 × 103 OSA细胞接种于96孔板,在包含10%血清的完全培养基中培养过夜,以测定50%抑制浓度。板在第5天采集,随后用0.001,0.005,0.01,0.05,0.1,0.5和1 μM Ganetespib处理并分析。荧光测量使用酶标仪在485 nm激发波长和530 nm发射检测波长下进行。相对细胞数以对照孔的百分比计算:样品吸光度/DMSO处理的细胞吸光度× 100。
实验图片 检测方法 检测指标 实验图片 PMID
Western blot EGFR / c-Met / IGF-1Rβ/ Akt / p-Akt / ERK / p-ERK p27(Kip1) / p21 (Cip1) / Cyclin D1 / Cyclin E / Cyclin B1 / CDK1 / CDK2 / CDK4 Survivin / Bcl-2 / Bcl-xl / Mcl-1 B-RAF / C-RAF / N-RAS HER2 / p-STAT3 / BIM CDK1 / Cyclin D1 / Cyclin B1 / p27 c-PARP / c-caspase 3 / caspase 8 / c-caspase 8 / caspase 9 / c-caspase 9 ErbB2 / pErbB2 / Src / pSrc / mTOR / pmTOR / Bad / pBad / GSK3 / pGSK3 Wee1 / p-Wee1 / Chk1 / p-Chk1 23418523
Growth inhibition assay Cell viability 23418523
体内研究(In Vivo)
体内研究活性 Ganetespib给药导致几种肿瘤异种移植模型的小鼠体内肿瘤显著缩减,且似乎毒性较低。此外,与tanespimycin相比,Ganetespib具有更好的肿瘤渗透性。[2]在恶性肥大细胞和OSA异种移植模型中,Ganetespib抑制体内肿瘤生长。 Ganetespib(25 mg/kg/day,3天)重复两个周期显著抑制肿瘤生长,%T/C值为18。Ganetespib能够被很好的耐受,载体对照和Ganetespib组相对于研究开始时的平均体重改变在第17天使分别为+0.3% 和-8.1%。[4]
动物实验 Animal Models 雌性严重的联合免疫缺陷(SCID)小鼠
Dosages 25 mg/kg/day,持续 3 天
Administration 尾部静脉注射
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02192541 Terminated
Neoplasms
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
December 2 2014 Phase 1
NCT02008877 Completed
Malignant Peripheral Nerve Sheath Tumors (MPNST)|Sarcoma
Sarcoma Alliance for Research through Collaboration|Synta Pharmaceuticals Corp.|United States Department of Defense
December 2013 Phase 1|Phase 2

化学信息&溶解度

分子量 364.4 分子式

C20H20N4O3

CAS号 888216-25-9 SDF Download Ganetespib (STA-9090) SDF
Smiles CC(C)C1=C(C=C(C(=C1)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)O)O
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 40 mg/mL ( (109.76 mM); DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Ethanol : 9 mg/mL

Water : 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。

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常见问题及建议解决方法

问题 1:
Does this inhibitor inhibit both isoforms of HSP90?

回答:
We don't have the information now and it is not very clear in the literature either. From following two references, it indicates that Ganetespib might be specific to the alpha form “Ganetespib binds to the ATP binding site of Hsp90 alpha with a Kd of 110 nM” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477583/

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