Prexasertib Mesylate Hydrate

Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate) is a potent, selective, ATP competitive CHK1 and CHK2 inhibitor, with a Ki of 0.9 nM for CHK1 and IC50s of <1 nM, 8 nM for CHK1 and CHK2, respectively. Prexasertib Mesylate Hydrate inhibits HT-29 CHK1 autophosphorylation (S296) and HT-29 CHK2 autophosphorylation (S516). Prexasertib Mesylate Hydrate shows potent anti-tumor activity, significantly abrogates the G2/M checkpoint in p53 deficient HeLa cells with an EC50 of 9 nM[1].

Signaling Pathways >> Cell Cycle/DNA Damage >> Checkpoint Kinase (Chk)

Research Areas >> Cancer

Chk1:0.9 nM (Ki)

Chk1:<1 nM (IC50)

Chk2:8 nM (IC50)

Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate) is an ATP competitive CHK1 inhibitor, with a Ki of 0.9 nM and an IC50 of <1 nM[1]. Prexasertib (LY2606368) shows high anti-tumor activity against U-2 OS, Calu-6 and HeLa cells (IC50, 3, 3, 37 nM, respectively), causes DNA damage during S-phase requiring CDC25A and CDK2 at 4 μM[1]. Prexasertib (0-20 nM) synergizes with olaparib (0-20 μM) to decrease cell viability in HGSOC cells[2].

Prexasertib (1, 3.3 or 10 mg/kg s.c.) is well tolerated, and significantly inhibits tumor inhibition in mice bearing Calu-6 xenograft tumors[1].

[1]. King C, et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-13.

[2]. Brill E, et al. Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer. Oncotarget. 2017 Oct 31;8(67):111026-111040.

LY2606368 | AZD7762 | CCT245737 | LY2603618 | CCT241533 hydrochloride | MK-8776(SCH 900776) | CHIR-124 | CHK2 INHIBITOR II | PF-477736 | CCT244747 | GDC-0575(ARRY-575) | CHK-IN-1 | CHK1 inhibitor | CHK1-IN-2