Berzosertib 已用于研究卵巢肿瘤、卵巢浆液性肿瘤、成人实体瘤、晚期实体瘤和晚期实体瘤等治疗的试验。

VE-822 has been used in trials studying the treatment of Ovarian Neoplasms, Ovarian Serous Tumor, Adult Solid Neoplasm, Advanced Solid Tumor, and Advanced Solid Neoplasm, among others.

和XTR单独作用相比,60 mg/kg VE-822和XTR联用使携带PSN-1和MiaPaCa-2肿瘤的小鼠中肿瘤生长到600 mm3的时间增加一倍.和Gem+XRT1联用相比,60 mg/kg VE-822添加到gemcitabine和XRT的组合中大大延长了PSN-1肿瘤小鼠中肿瘤生长延迟.与XRT1相比,60 mg/kg VE-822和XRT1联用使肿瘤摄取增加44％,这表明VE-822增加了γH2AX磷酸化和XRT引起的DNA损伤持续性.60 mg/kg VE-822抑制小鼠PSN-1肿瘤中丝氨酸345-Chk1的磷酸化.

80 nM VE-822单独使用增加MiaPaCa-2和PSN-1细胞停留在G1期的比率。80 nM VE-822消除MiaPaCa-2和PSN-1细胞中富含XRT的G2/M期部分。VE-822单独作用不大,而80 nM VE-822与XRT和/或gemcitabine联用则增强PSN-1细胞中的早期和晚期细胞凋亡。VE-822增加对与pChk1 Ser345阻断相关的DNA损伤剂的肿瘤应答。VE-822（80 nM）减弱ATR信号传导途径并降低肿瘤细胞对XRT和吉西他滨的应答的存活率。在正常细胞中,80 nM VE-822减弱ATR信号通路强度,但并没有增强辐射和gemcitabine杀伤正常细胞的能力。

A375 cells are pre-treated with 1 μM JNK-IN-8 for the indicated amounts of time. Remove the medium and wash 3 times with PBS. Resuspend the cell pellet with 1 mL Lysis Buffer (1% NP-40, 1% CHAPS, 25 mM Tris, 150 mM NaCl, Phosphatase Inhibitor Cocktail, and Protease Inhibitor Cocktail). Rotate end-to-end for 30 min at 4°C. Lysates are cleared by centrifugation at 14000 rpm for 15 min in the Eppendorf. The cleared lysates gel filtered into Kinase Buffer (0.1% NP-40, 20 mM HEPES, 150 mM NaCl, Phosphatase Inhibitor Cocktail, Protease Inhibitor Cocktail) using Bio-Rad 10DG colums. The total protein concentration of the gel-filtered lysate should be around 5-15 mg/mL. Cell lysate is labeled with the probe from ActivX at 5 μM for 1 hour. Samples are reduced with DTT, and cysteines are blocked with iodoacetamide and gel filtered to remove excess reagents and exchange the buffer. Add 1 volume of 2X Binding Buffer (2% Triton-100, 1% NP-40, 2 mM EDTA, 2X PBS) and 50 μL streptavidin bead slurry and rotate end-to-end for 2 hours, centrifuge at 7000 rpm for 2 min. Wash 3 times with 1X Binding Buffer and 3 times with PBS. Add 30 μL 1X sample buffer to beads, heat samples at 95°C for 10 min. Run samples on an SDS-PAGE gel at 110V. After transferred, the membrane is immunoblotted with JNK antibody[1].

VE-822 is dissolved in DMSO and stored, and then diluted with appropriate media before use[1]. Gemcitabine (10 nM) is added 24 h pre-XRT and is replaced with fresh medium before addition of VE-822. PSN-1 cells are treated with VE-822 (80 nM) for 1 h before, through to 18 h after, XRT (6 Gy). Apoptosis is analyzed 48 h after XRT by flow cytometry using an Annexin V-FITC kit with PI[1].

1232416-25-9

C24H25N5O3S

463.55

VX-970;VE-822

DMSO:34 mg/mL (73.3 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years