Prexasertib mesylate  (Synonyms: LY2606368 mesylate)

Prexasertib mesylate (LY2606368 mesylate) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K_i of 0.9 nM and an IC₅₀ of <1 nM. Prexasertib mesylate inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib mesylate causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib mesylate shows potent anti-tumor activity^[1][2].

Prexasertib (LY2606368) mesylate inhibits MELK (IC₅₀=38 nM), SIK (IC₅₀=42 nM), BRSK2 (IC₅₀=48 nM), ARK5 (IC₅₀=64 nM). Prexasertib mesylate requires CDC25A and CDK2 to cause DNA damage^[1].
Prexasertib mesylate (33, 100 nM; for 7 hours) results in DNA damage during S-phase in HeLa cells^[1].
Prexasertib mesylate (8-250 nM; pre-treated for 15 minutes) inhibits CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) in HT-29 cells^[1].
Prexasertib mesylate (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^[1].
Prexasertib mesylate (33 nM; for 12 hours) causes chromosomal fragmentation in HeLa cells. Prexasertib mesylate (100 nM; 0.5 to 9 hours) induces replication stress and depletes the pool of available RPA2 for binding to DNA^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Prexasertib mesylate (1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) causes growth inhibition in tumor xenografts^[1].
Prexasertib mesylate (15 mg/kg; SC) causes CHK1 inhibition in the blood and the phosphorylation of both H2AX (S139) and RPA2 (S4/S8)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

461.49

C₁₉H₂₃N₇O₅S

1234015-55-4

N#CC1=NC=C(NC2=NNC(C3=C(OC)C=CC=C3OCCCN)=C2)N=C1.CS(=O)(O)=O

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• [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.  [Content Brief]

  [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.  [Content Brief]