Luminespib (VER-52296) is an HSP90 inhibitor that inhibits HSP90α and HSP90β (IC50=7.8/21 nM). Luminespib has antitumor activity and is used in studies of head and neck tumors, among others.

HSP90 β:21 nM (cell free), HSP90 α:7.8 nM (cell free)

方法：HER2 阳性肿瘤细胞 OE19、ESO26、N87、OE33 和 SNU-216 用 Luminespib (1-1000 nM) 处理 72 h，通过 CellTiter-Glo luminescent cell viability assay 测定细胞活力。
结果：Luminespib 显示出强大的抗肿瘤效果，对 OE19、ESO26、N87、OE33 和 SNU-216 细胞的 IC50 分别为 20 nM、50 nM、80 nM、40 nM、50 nM。[1]
方法：HCT116 细胞用 Luminespib (80 nmol/L) 处理 8-72 h，通过 Western Blot 检测靶点蛋白表达水平。
结果：HCT116 细胞暴露于 Luminespib 导致 CRAF 和 ERBB2 的快速消耗以及伴随的 HSP72的诱导。[2]

方法：为检测体内抗肿瘤活性，将 Luminespib (75-50 mg/kg) 腹腔注射给携带 WM266.4 异种移植物的 NCr athymic 小鼠，每天一次，持续 11 天。
结果：Luminespib 显著抑制了肿瘤生长速率，将对照组第 11 天的肿瘤平均重量从 252±19 mg 降低到 78±6 mg。第 11 天的肿瘤样本显示了耗竭 ERBB2 和 CDK4 的 HSP90 抑制特征，并诱导了 HSP72。[2]

Cell lines were grown in DMEM/10% FCS, 2 mmol/L glutamine, and nonessential amino acids in a humidified atmosphere of 5% CO2 in air. All lines were free of Mycoplasma. Cell proliferation was determined using the sulforhodamine B (SRB) assay for tumor cells and prostate epithelial cells, the WST-1 assay for MCF10A and HB119, or an alkaline phosphatase assay for HUVEC and HDMEC. GI50 was the compound concentration inhibiting cell proliferation by 50% compared with vehicle controls. Cell cycle analysis was as described. Active caspase-3/7 was measured using a homogenous caspase assay kit [1].

In vivo, pharmacokinetic studies in female NCr athymic mice bearing WM266.4 human melanoma xenografts were essentially as described. NVP-AUY922 was dissolved in DMSO and diluted in sterile saline/Tween 20. A single dose of 50 mg/kg NVP-AUY922 was given i.v. or i.p. and groups of three animals were taken at intervals for pharmacokinetic analyses [1].