Prexasertib dimesylate (LY2606368 dimesylate) 是一种选择性的，ATP 竞争性的第二代细胞周期检测点激酶 1 (CHK1) 抑制剂，K_i 为 0.9 nM，IC₅₀ 为 <1 nM。Prexasertib dimesylate 抑制 CHK2 (IC₅₀=8 nM) 和 RSK1 (IC₅₀=9 nM)。Prexasertib dimesylate 引起双链 DNA 断裂和复制突变，导致细胞凋亡 (apoptosis)。Prexasertib dimesylate 显示有效的抗肿瘤活性。

Prexasertib dimesylate (LY2606368 dimesylate) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K i of 0.9 nM and an IC 50 of <1 nM. Prexasertib dimesylate inhibits CHK2 (IC 50 =8 nM) and RSK1 (IC 50 =9 nM). Prexasertib dimesylate causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dimesylate shows potent anti-tumor activity.

Solid

Chk1 0.9 nM (Ki) Chk1 <1 nM (IC50)pa

Prexasertib dimesylate (LY2606368 dimesylate) inhibits MELK (IC50=38 nM), SIK (IC50=42 nM), BRSK2 (IC50=48 nM), ARK5 (IC50=64 nM). Prexasertib dimesylate requires CDC25A and CDK2 to cause DNA damage.
Prexasertib dimesylate (33, 100 nM; for 7 hours) results in DNA damage during S-phase in HeLa cells.
Prexasertib dimesylate (8-250 nM; pre-treated for 15 minutes) inhibits CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) in HT-29 cells.
Prexasertib dimesylate (4 nM; 24 hours) results in a large shift in cell-cycle populations from G1 and G2-M to S-phase with an accompanied induction of H2AX phosphorylation in U-2 OS cells.
Prexasertib dimesylate (33 nM; for 12 hours) causes chromosomal fragmentation in HeLa cells. Prexasertib dimesylate (100 nM; 0.5 to 9 hours) induces replication stress and deple

Prexasertib dimesylate (LY2606368 dimesylate; 1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) causes growth inhibition in tumor xenografts.
Prexasertib dimesylate (15 mg/kg; SC) causes CHK1 inhibition in the blood and the phosphorylation of both H2AX (S139) and RPA2 (S4/S8).
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

[1]. King C, et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-1
[2]. Yin Y, et al. Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer. Am J Cancer Res. 2017 Mar 1;7(3):473-483.

In Vitro: DMSO : 100 mg/mL (179.34 mM; Need ultrasonic)H₂O : 50 mg/mL (89.67 mM; Need ultrasonic)配制储备液