Rabusertib (LY2603618)

Catalog No.S2626 Synonyms: IC-83

For research use only.

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

CAS No. 911222-45-2

Selleck's Rabusertib (LY2603618) has been cited by 67 publications

Purity & Quality Control

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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

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, such as gemcitabine. [2] LY2603618 treatment impairs DNA synthesis, increases DNA damage (via mitotic defects), induces apoptosis, and has synergistic activity with pemetrexed, especially in p53 mutant tumor cells. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BT474 MXnLbY5ie2ViYYPzZZk> M{WzTlEh|ryP Ml61SG1UVw>? MorSbY5pcWKrdIOgVE1EUEtzIHzleoVtew>? NY\ZWJhzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5NVc{PzhpPkKzPVE4Ozd6PD;hQi=>
MCF7 Mkj4T4lv[XOnIHHzd4F6 MnriNUDPxE1? MW\EUXNQ M2GxfIlvcGmkaYTzJHAuS0iNMTDs[ZZmdHN? MljqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7MUezO|goRjJ|OUG3N|c5RC:jPh?=
Hela MVrLbY5ie2ViYYPzZZk> M4L5WFM{ODBibl2= MVnEUXNQ MkXvbY5pcWKrdIOgR4hsOSCjY4Tpeol1gQ>? NHvwSYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEGxOFEzPCd-MkSxNVQyOjR:L3G+
Calu6 NF[4RVRMcW6jc3WgZZN{[Xl? M{\4T|M{ODBibl2= NGi5e25FVVOR NWjzUYh6cW6qaXLpeJMhS2itMTDhZ5Rqfmm2eR?= NVjrd2c{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxNVQyOjRpPkK0NVE1OTJ2PD;hQi=>
A549 MWnGeY5kfGmxbjDhd5NigQ>? M3zyRZ4yOCEQvF2= M1izNWROW09? M4DzcYlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= Mli1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MkiyNFUoRjJ2OUK4NlA2RC:jPh?=
H1299 NGqzUYZHfW6ldHnvckBie3OjeR?= MleyglExKM7:TR?= MW\EUXNQ M4LBfIlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= Mnm3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MkiyNFUoRjJ2OUK4NlA2RC:jPh?=
A549 MV;GeY5kfGmxbjDhd5NigQ>? M3TsdZ4zOCEQvF2= NUfTemlJTE2VTx?= M3jqc4FkfGm4YYTld{BFVkFiZHHtZYdmKHOnboPvdkBscW6jc3Xz MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl{OEKwOUc,OjR7MkiyNFU9N2F-
H1299 MlrHSpVv[3Srb36gZZN{[Xl? MUT+NlAh|ryP NV:4NZRxTE2VTx?= M4HrOYFkfGm4YYTld{BFVkFiZHHtZYdmKHOnboPvdkBscW6jc3Xz Mn[0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MkiyNFUoRjJ2OUK4NlA2RC:jPh?=
A549 MoThRZBweHSxc3nzJIF{e2G7 NF\iW5d,OjBizszN NVGwd5QyTE2VTx?= NUm2dFFscW6mdXPld{BieG:ydH;zbZM> NGT2WXI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmyPFIxPSd-MkS5NlgzODV:L3G+
H1299 M3r4TGFxd3C2b4Ppd{Bie3OjeR?= MXP+NlAh|ryP MYPEUXNQ NGTNV3lqdmS3Y3XzJIFxd3C2b4Ppdy=> MlfpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MkiyNFUoRjJ2OUK4NlA2RC:jPh?=
A549 MV7DfZRwgGmlaYT5JIF{e2G7 M3jYS54zOCEQvF2= MU\EUXNQ MnP5bY5lfWOnczDheZRweGijZ4m= NGnuclc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmyPFIxPSd-MkS5NlgzODV:L3G+
H1299 NX;zS5drS3m2b4jpZ4l1gSCjc4PhfS=> MmTEglIxKM7:TR?= NEizcFZFVVOR NWrNW|RYcW6mdXPld{BifXSxcHjh[5k> MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl{OEKwOUc,OjR7MkiyNFU9N2F-
A549 NXjoVI1WTnWwY4Tpc44h[XO|YYm= MXH+NlAh|ryP NY\nSZk4TE2VTx?= Ml7RbY5kemWjc3XzJGpPUyCjbnSgdFM5KE2DUFugdIhwe3Cqb4L5cIF1cW:w NW\2NJpzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NlgzODVpPkK0PVI5OjB3PD;hQi=>
H1299 M2C0Z2Z2dmO2aX;uJIF{e2G7 MXv+NlAh|ryP NYjIO|RITE2VTx?= MVzpcoNz\WG|ZYOgTm5MKGGwZDDwN|ghVUGSSzDwbI9{eGixconsZZRqd25? MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl{OEKwOUc,OjR7MkiyNFU9N2F-
OHS-50 NVHueZR[eUiWUzDhd5NigQ>? NXm5flBueUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=> NVzkO|R2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2 NGjtNndyUFSVIHHzd4F6 NUPIR2hoeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM> NH:4Wmg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-MC MkjTdWhVWyCjc4PhfS=> NVfrdG5teUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> NX[4W3FPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB-EBc1 NF7vfpJyUFSVIHHzd4F6 M1\MepFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz NEK5bGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
LAN-5 M2nPTJFJXFNiYYPzZZk> NYLWfI9weUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz NE\QWnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Assay
Methods Test Index PMID
Western blot p-Chk1 / Chk1 / CDC25A ; PARP / CF-PARP / p-CDC25C / p-CDK1 / p-CDK2 29326282 25458954
Growth inhibition assay Cell viability 29326282
In vivo In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. [3]

Protocol (from reference)

Cell Research:

[4]

  • 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.

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMSO+ 40% PEG 300+5% Tween 80 +50% ddH2O
For best results, use promptly after mixing.

1mg/mL

Chemical Information

Molecular Weight 436.3
Formula

C18H22BrN5O3

CAS No. 911222-45-2
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OCC3CNCCO3

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01341457 Completed Drug: LY2603618|Drug: Gemcitabine Solid Tumors Eli Lilly and Company May 2011 Phase 1
NCT01296568 Completed Drug: LY2603618|Drug: Pemetrexed|Drug: Gemcitabine Advanced Cancer Eli Lilly and Company February 2011 Phase 1
NCT01139775 Completed Drug: Pemetrexed|Drug: Cisplatin|Drug: LY2603618 Non Small Cell Lung Cancer Eli Lilly and Company February 2011 Phase 1|Phase 2
NCT00988858 Completed Drug: LY2603618|Drug: Pemetrexed Non Small Cell Lung Cancer Eli Lilly and Company November 2009 Phase 2
NCT00839332 Completed Drug: LY2603618|Drug: Gemcitabine Pancreatic Neoplasms Eli Lilly and Company February 2009 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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