Product Name:LY2606368 dihydrochloride;Prexasertib dihydrochloride
LY2606368 is a potent and selective ATP competitive inhibitor of Chk1, with an IC50 of <1 nM, and also inhibits CHK2, with an IC50 of 8 nM. LY2606368 has an EC50 of 1 nM for CHK1 activity through autophosphorylation of serine 296 and <31 nM for HT-29 CHK2 autophosphorylation (S516). LY2606368 potently abrogates the G2-M checkpoint activated by doxorubicin in p53-deficient HeLa cells with an EC50 of 9 nM. However, 100 nM LY2606368 does not inhibit PMA-stimulated RSK but instead weakly stimulates phosphorylation of S6 on serines 235/236. 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 (4 nM) 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. LY2606368 (25 μM) exhibits inhibitory activities against proliferation of AGS and MKN1 cells. LY2606368 (20 nM) inhibits HR repair capacity DR-GFP cells. LY2606368 (5 nM) in combination with PARP inhibitor BMN673, displays synergistic anticancer effects in gastric cancer cells.