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
CAS: 888216-25-9
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Ganetespib (STA-9090)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 |
|---|---|---|---|---|---|
| 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 | ||
| 点击查看更多细胞系数据 | |||||
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 |
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| 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) | |||
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体外溶解度 |
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 (24.69 mM) Water : 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:
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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