VER 155008 is a potent, adenosine-derived inhibitor of the heat shock protein 70 (Hsp70) family, with IC50 values of 0.5μM, 2.6μM, and 2.6μM against Hsp70, heat shock cognate protein 70 (Hsc70), and glucose-regulated protein 78 (Grp78), respectively[1]. VER 155008 exerts its effects by inhibiting Hsp70 ATPase activity, inducing cell cycle arrest, apoptosis, and tumor-specific cell death, and is commonly used in anti-cancer (e.g., prostate and breast cancer) and antiviral research[2,3,4].
In vitro, treatment with VER 155008 (20μM) for 48h in 211H and H28 cells significantly increased the proportion of cells in the G1 phase (from 69.9% to 82.7% in 211H cells; from 77% to 85.2% in H28 cells)[5]. VER 155008 (25μM) treatment in A549 and H1975 cells for 2 days significantly reduced the percentage of 5-bromo-2'-deoxyuridine (BrdU)-positive cells, indicating inhibition of cell proliferation[6].
In vivo, intraperitoneal injection of VER 155008 (40mg/kg; once daily) for two weeks in PC12 tumor-bearing nude mice significantly reduced tumor volume and tumor weight[7]. A single intravenous dose of VER 155008 (25mg/kg) in BALB/c mice resulted in a plasma half-life of 0.6h and a clearance rate of 49mL/min/kg[1].
References:
[1] MASSEY A J, WILLIAMSON D S, BROWNE H, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells[J]. Cancer Chemotherapy and Pharmacology, 2010, 66(3): 535-545.
[2] BUDINA-KOLOMETS A, BALABURSKI G M, BONDAR A, et al. Comparison of the activity of three different HSP70 inhibitors on apoptosis, cell cycle arrest, autophagy inhibition, and HSP90 inhibition[J]. Cancer Biology & Therapy, 2014, 15(2): 194-199.
[3] WENG J R, HUA C H, CHEN C H, et al. Anti-apoptotic activity of Japanese encephalitis virus NS5 protein in human medulloblastoma cells treated with interferon-β[J]. Journal of Microbiology, Immunology and Infection, 2018, 51(4): 456-464.
[4] YU B, YANG H, ZHANG X, et al. Visualizing and quantifying the effect of the inhibition of HSP70 on breast cancer cells based on laser scanning microscopy[J]. Technology in Cancer Research & Treatment, 2018, 17: 1533033818785274.
[5] SAKAI K, INOUE M, MIKAMI S, et al. Functional inhibition of heat shock protein 70 by VER‐155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism[J]. Thoracic Cancer, 2021, 12(4): 491-503.
[6] WEN W, LIU W, SHAO Y, et al. VER-155008, a small molecule inhibitor of HSP70 with potent anti-cancer activity on lung cancer cell lines[J]. Experimental Biology and Medicine, 2014, 239(5): 638-645.
[7] XU F, LIN D, JIANG W, et al. HSP70 inhibitor VER155008 suppresses pheochromocytoma cell and xenograft growth by inhibition of PI3K/AKT/mTOR and MEK/ERK pathways[J]. International Journal of Clinical and Experimental Pathology, 2019, 12(7): 2585.
VER 155008是一种强效的，源自腺苷的热休克蛋白70（Hsp70）家族抑制剂，对Hsp70、热休克同源蛋白70（Hsc70）和葡萄糖调节蛋白78（Grp78）的IC50值分别为0.5μM、2.6μM和2.6μM[1]。VER 155008通过抑制Hsp70 ATP酶活性，诱导细胞周期停止、细胞凋亡和肿瘤特异性细胞死亡发挥作用，通常用于抗癌（如前列腺癌和乳腺癌等）和抗病毒研究[2,3,4]。
在体外，VER 155008（20μM）处理211H和H28细胞48h，G1期细胞比例显著增加（211H从69.9%增加到82.7%；H28从77%增加到85.2%）[5]。VER 155008（25μM）处理A549和H1975细胞2天，5-bromo-2’-deoxyuridine（BrdU）阳性细胞百分比显著降低，细胞增殖被抑制[6]。
在体内，VER 155008（40mg/kg; once daily）通过腹腔注射治疗PC12荷瘤裸鼠2周，肿瘤体积显著减小且肿瘤重量也显著减轻[7]。VER 155008（25mg/kg）通过单次静脉注射处理BALB/c小鼠，血浆半衰期为0.6h，清除率为49mL/min/kg[1]。