化合物Berzosertib T2669

Product Introduction
Bioactivity


英文名: Berzosertib

描述: Berzosertib (VE-822) 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。

细胞实验: 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].

激酶实验: 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].

体外活性: 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.

体内活性: 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。

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 7.86 mg/mL (16.95 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)


关键字: VE 822 | VX 970 | VX970 | VE822 | Berzosertib

相关产品: KU 59403 | Schisandrin B | Garcinone C | A011 | ATM Inhibitor-9 | AZD0156 | azd1390 | M3541 | Ro 90-7501 | Wortmannin

相关库: Anti-Aging Compound Library | Drug Repurposing Compound Library | HIF-1 Signaling Pathway Compound Library | Anti-Cancer Drug Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Highly Selective Inhibitor Library | Anti-Cancer Active Compound Library | Stem Cell Differentiation Compound Library | NO PAINS Compound Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途