VER-155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78, respectively, >100-fold selectivity over HSP90.

GRP78:2.6 μM, HSP70:0.5 μM, HSC70:2.6 μM

VER-155008抑制人类乳腺癌和结肠癌细胞系BT474、MB-468、HCT116和HT29的增殖，GI50范围为5.3-14.4 μM，并在HCT116和BT474细胞中诱导Hsp90客体蛋白降解。[1] 在8505C和FRO细胞中，VER-155008以时间和剂量依赖的方式降低细胞活性并提高死亡细胞比例。[2] VER-155008导致剂量依赖性的抑制细胞因子依赖的AML细胞增殖。[3] VER-155008在A549和H1975细胞中有效抑制细胞增殖。[4]

在携带HCT116肿瘤的小鼠中，VER-155008（25或40 mg/kg，i.v.）表现出快速的代谢和清除作用，并且其在肿瘤中的浓度低于预测的药理活性水平。[1]

Hsc70, Hsp70 and Grp78 ?uorescence polarisation (FP) assay: The FP assay for Hsp70 is conducted in aqueous buffer consisting of 100 mM Tris pH 7.4, 150 mM KCl and 5 mM CaCl2, in a final assay volume of 100 μl, using 96 well black polystyrene high bind plates with a Fusion plate reader. N6-(6-amino)hexyl-ATP-5-FAM and the in-house protein preparation of GST-HSP70 3-382 have final concentrations in the assay of 20 nM and 400 nM, respectively. Compounds are tested as 10-point IC50s, with a final DMSO concentration of 5%. Assay mixtures are incubated for 3 h prior to reading on the Fusion (ex 485 nm; em 535 nm). The data is fitted using a 4 parameter logistical data model by XLFit 4. The FP assay for Hsc70 and Grp78 is carried out as described for Hsp70 using the same N6 -(6-amino)hexyl-ATP-5-FAM as the FP probe with the following modi?cations. For Hsc70, the protein and probe concentrations are 0.3 μM and 20 nM, respectively with a 30 min incubation at 22℃ while for Grp78, the protein and probe concentrations are 2 μM and 10 nM, respectively with a 2 h incubation at 22℃. The KD for the FAM-ATP probe was 0.24 μM for Hsc70 and 2 μM for Grp78.

All cell lines are grown in DMEM/10% FCS with GlutaMAX-I in a humidified atmosphere of 5% CO2 in air. Cell proliferation is determined using the sulforhodamine B (SRB) assay.(Only for Reference)