LY2603618

Description

LY2603618 (911222-45-2) is a potent (IC50?= 7nM) and selective (>1000x over Chk2) Checkpoint kinase 1 (Chk1) inhibitor.1?Chk1 is an important regulator of the DNA damage response – combination treatment of LY2603618 with other chemotherapeutic agents significantly increased tumor growth inhibition when compared to chemotherapeutic alone.2,3,4?LY2603618 caused a dramatic suppression of cell growth in MCF-7 and MDA-MB-231 human breast cancer cells?via?Chk1 inhibition induced upregulation of replication stress caused by oncogenes.5

The Uses of LY2603618

LY2603618 is a selective Chk1 inhibitor that can treat idiopathic pulmonary fibrosis.

What are the applications of Application

LY2603618 is a selective Chk1 inhibitor

Definition

ChEBI: 1-[5-bromo-4-methyl-2-[[(2S)-2-morpholinyl]methoxy]phenyl]-3-(5-methyl-2-pyrazinyl)urea is a member of ureas.

Biological Activity

Rabusertib (LY2603618, IC-83) is a highly selective inhibitor of Chk1 with potential antitumor activity in cell-free assays, IC50=7 nM, potency against Chk1 versus multiple other protein kinases tested 100 times higher. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines.

in vivo

experiment was carried out to determine the combining effect of ly2603618 with other chemotherapy[2] . in mice xenograft model that inculated with calu-6 lung cancer cell, combining administration of injected gemcitabine 150 mg/kg and orally uptake ly2603618 (200 mg/kg) resulted in increased dna damage of tumour, as was demonstrated by a 2-fold increase in chk1 s345 phosphorylation in comparison with mice treated with gemcitabine alone[2].

Storage

Store at -20°C

References

1) King?et al.?(2014),?Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor; Invest. New Drugs,?32?213 2) Calvo?et al.?(2014),?Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer; Invest. New Drugs,?32?955 3) Calvo?et al. (2016),?Phase I Study of CHK1 Inhibitor LY2603618 in Combination with Gemcitabine in Patients with Solid Tumors; Oncology,?91?251 4) Zhao?et al.?(2016),?Inhibition of CHK1 enhances cell death induced by the Bcl-1-selective inhibitor ABT-199 in acute myeloid leukemia cells; Oncotarget,?7?34785 5) Zhang?et al.?(2016),?Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stress; Oncotarget,?7?34688