Home Cell Cycle Chk inhibitor - Apoptosis related activator - Autophagy activator Rabusertib (LY2603618) For research use only.

Rabusertib (LY2603618)

Synonyms: IC-83

Rabusertib (LY2603618, IC-83) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines.

Rabusertib (LY2603618) Chemical Structure

Rabusertib (LY2603618) Chemical Structure

CAS No. 911222-45-2

Purity & Quality Control

Rabusertib (LY2603618) Related Products

Signaling Pathway

Chk Signaling Pathways

Chk Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BT474 Kinase assay 1 μM DMSO inhibits P-CHK1 levels 23917378
MCF7 Kinase assay 1 μM DMSO inhibits P-CHK1 levels 23917378
Hela Kinase assay 3300 nM DMSO inhibits Chk1 activity 24114124
Calu6 Kinase assay 3300 nM DMSO inhibits Chk1 activity 24114124
A549 Function assay ~10 μM DMSO induces cell cycle arrest 24928205
H1299 Function assay ~10 μM DMSO induces cell cycle arrest 24928205
A549 Function assay ~20 μM DMSO activates DNA damage sensor kinases 24928205
H1299 Function assay ~20 μM DMSO activates DNA damage sensor kinases 24928205
A549 Apoptosis assay ~20 μM DMSO induces apoptosis 24928205
H1299 Apoptosis assay ~20 μM DMSO induces apoptosis 24928205
A549 Cytoxicity assay ~20 μM DMSO induces autophagy 24928205
H1299 Cytoxicity assay ~20 μM DMSO induces autophagy 24928205
A549 Function assay ~20 μM DMSO increases JNK and p38 MAPK phosphorylation 24928205
H1299 Function assay ~20 μM DMSO increases JNK and p38 MAPK phosphorylation 24928205
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
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Biological Activity

Description Rabusertib (LY2603618, IC-83) is a highly selective Chk1 inhibitor with potential anti-tumor activity in a cell-free assay. IC50=7 nM, showing approximately 100-fold more potent against Chk1 than against any of the other protein kinases evaluated. Rabusertib (LY2603618) induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Rabusertib (LY2603618) induces bak-dependent apoptosis in AML cell lines.
Targets
Chk1 [1]
(Cell-free assay)
7 nM
In vitro
In vitro

Chk1 is an ATP-dependent serine-threonine kinase and a key component in the DNA replication-monitoring checkpoint system activated by double-stranded breaks (DSBs). Chk1 contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. By inhibiting the activity of chk1, LY2603618 prevents the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. However, preclinical data involving LY2603618 has not been published until now. [1]

Inhibition of Chk1 is predicted to enhance the effects of antimetabolites. [2]

LY2603618 treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity, especially in p53 mutant tumor cells. [3]
Cell Research Cell lines A549 and H1299 cell
Concentrations 5 or 10 μM
Incubation Time 24 h
Method

Cells were treated with LY2603618 and DMSO as a control. After trypsinization, cells were fixed in 70 % ethanol at 4 C overnight. The cells were washed twice with PBS and incubated for 30 min in the dark in PBS containing propidium iodide (PI) and RNase A. Stained cells were analyzed by a FACScan flow cytometry and CellQuest analysis software.
Experimental Result Images Methods Biomarkers Images PMID
Western blot PARP / CF-PARP / p-CDC25C / p-CDK1 / p-CDK2 p-Chk1 / Chk1 / CDC25A 25458954
Growth inhibition assay Cell viability 29326282
In Vivo
In vivo

In xenograft models, LY2603618 delays tumor growth when given in combination. [3]
Animal Research Animal Models Male Wistar rats
Dosages 50 mg/kg
Administration i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01341457 Completed
Solid Tumors
Eli Lilly and Company
 May 2011 Phase 1
NCT01296568 Completed
Advanced Cancer
Eli Lilly and Company
 February 2011 Phase 1
NCT01139775 Completed
Non Small Cell Lung Cancer
Eli Lilly and Company
 February 2011 Phase 1|Phase 2
NCT00988858 Completed
Non Small Cell Lung Cancer
Eli Lilly and Company
 November 2009 Phase 2
NCT00839332 Completed
Pancreatic Neoplasms
Eli Lilly and Company
 February 2009 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 436.3 Formula

C18H22BrN5O3
CAS No. 911222-45-2 SDF Download Rabusertib (LY2603618) SDF
Smiles CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OCC3CNCCO3
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 22 mg/mL ( (50.42 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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