Prexasertib 是一种具有潜在抗肿瘤活性的检查点激酶 1 抑制剂。它可引起双链 DNA 断裂和复制突变,导致细胞凋亡。
产品描述
Prexasertib is an inhibitor of checkpoint kinase 1 (chk1) with potential antineoplastic activity.
体外活性
LY2606368 potently abrogates the G2-M checkpoint activated by doxorubicin in p53-deficient HeLa cells(EC50=9 nM). LY2606368 is a potent and selective ATP competitive inhibitor of Chk1(IC50<1 nM), and also inhibits CHK2(IC50=8 nM).
体内活性
In xenograft tumor models, LY2606368 (15 mg/kg, s.c.) significantly inhibits tumor growth with less animal weight loss.
细胞实验
LY2606368 is broadly antiproliferative with IC50s of 3 nM, 3 nM, 10 nM, 37 nM, and 68 nM against U-2 OS, Calu-6, HT-29, HeLa, and NCI-H460 cell lines, respectively. LY2606368 (25 μM) exhibits inhibitory activities against proliferation of AGS and MKN1 cells. LY2606368 (20 nM) inhibits HR repair capacity DR-GFP cells.
动物实验
LY2606368 is formulated in vehicle consisting of 20% Captisol.Female CD-1 nu-/nu- mice (26-28 g) are used for this study. Tumor growth is initiated by subcutaneous injection of 1×106 Calu-6 cells in a 1:1 mixture of serum-free growth medium and Matrigel in the rear flank of each subject animal. When tumor volumes reach approximately 150 mm3 in size, the animals are randomized by tumor size and body weight, and placed into their respective treatment groups. Vehicle consisting of 20% Captisol pH4 or LY2606368 is administered by subcutaneous injection in a volume of 200 μL. Four, eight, 12, 24, and 48 hours after drug administration, blood for plasma drug exposure is extracted via cardiac puncture and assayed on a Sciex API 4000 LC/MS-MS system. The xenograft tissue is promptly removed and prepared. Lysates are analyzed by immunoblot analysis for protein phosphorylation levels. Group means, SEs and P values are calculated using Kronos.
Cas No.
1234015-52-1
分子式
C18H19N7O2
分子量
365.397
别名
LY2606368;5-[[5-[2-(3-氨基丙氧基)-6-甲氧基苯基]-1H-吡唑-3-基]氨基]-2-吡嗪甲腈
储存和溶解度
DMSO:60 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years