Rabusertib (LY2603618)

Catalog No.S2626 Synonyms: IC-83

Rabusertib (LY2603618) Chemical Structure

Molecular Weight(MW): 436.3

Rabusertib (LY2603618) 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.

Size Price Stock Quantity  
In DMSO USD 300 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock
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Cited by 18 Publications

7 Customer Reviews

  • MK-1775 and LY2603618 synergize to induce apoptosis in AML cell lines and primary patient samples. U937 and CTS cells were treated for 8 h. Whole cell lysates were subjected to Western blotting and probed with anti-γH2AX, -pCHK1, -p-cdc25c, -p-CDK1, -p-CDK2, -CDK1, or -β-actin antibody. Densitometry measurements, as described in the Materials and methods section, are shown below the corresponding Western blot.

    J Hematol Oncol 2014 7, 53. Rabusertib (LY2603618) purchased from Selleck.

  • BxPC-3 cells were treated with vehicle control, MK-1775 (MK), LY2603618 (LY) or MK-1775 plus LY2603618 for 48 h. Protein extracts were subjected to Western blotting and probed with anti-PARP, -p-CHK1, -CHK1, -p-CDC25C, -p-CDK1, -CDK1, -p-CDK2, -CDK2, -γH2AX, or -β-actin antibody.

    Cancer Lett 2014 10.1016/j.canlet.2014.10.015. Rabusertib (LY2603618) purchased from Selleck.

  • Biomarker changes induced in response to gemcitabine plus Chk1 inhibitor treatment in HT29 colon carcinoma cells. HT29 colon cancer cells were exposed to 50 nM gemcitabine (+) for 16 hours followed by increasing concentrations of Chk1 inhibitor for a further 24 hours. Protein expression was characterized by immunoblotting.

    BMC Cancer 2014 14, 483. Rabusertib (LY2603618) purchased from Selleck.

  • C6 cell was trypsinized and plated at 30% confluence in DMEM. 16 hours later, LY2603618 was added at final concentrations of 0, 1, 5, 10 and 20uM. Another 24 hours later, cells were harvested in RIPA with protease and phosphatase inhibitor cocktail. Total protein concentration was measured by BCA method. Lysates equivalent to 20ug total protein were subject to Western Blot, using pS345-CHK1, g-H2AX and beta-actin (internal control) antibodies.

    Customer W, F. Z. Rabusertib (LY2603618) purchased from Selleck.

  • Hela cell was trypsinized and plated at 30% confluence in DMEM. 16 hours later, LY2603618 was added at final concentrations of 0, 5, 10 and 25uM. Another 24 hours later, cells were harvested in RIPA with protease and phosphatase inhibitor cocktail. Total protein concentration was measured by BCA method. Lysates equivalent to 20ug total protein were subject to Western Blot, using total- CHK1, pS345-CHK1 and beta-actin (internal control) antibodies.

    Rabusertib (LY2603618) purchased from Selleck.

  • (E) EW8 cells were treated with 50 nM gemcitabine in combination with increasing doses of prexasertib, LY2603618, or MK-8776 for 6 hours. Cell lysates were then collected and blotted for p-CHK1-296.

    Mol Cancer Ther, 2018, 17(12):2676-2688. Rabusertib (LY2603618) purchased from Selleck.

  • Oncol Rep, 2018, 39(3):1322-1330. Rabusertib (LY2603618) purchased from Selleck.

Purity & Quality Control

Choose Selective Chk Inhibitors

Biological Activity

Description Rabusertib (LY2603618) 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.
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 MX3LbY5ie2ViYYPzZZk> MYKxJO69VQ>? MX;EUXNQ M1rIUYlvcGmkaYTzJHAuS0iNMTDs[ZZmdHN? NUD2c256OjN7MUezO|g>
MCF7 NX\yZWNZU2mwYYPlJIF{e2G7 MnrzNUDPxE1? NH7GbWxFVVOR NGC1cldqdmirYnn0d{BRNUOKS{GgcIV3\Wy| MUOyN|kyPzN5OB?=
Hela NVrpPXMxU2mwYYPlJIF{e2G7 M{XQXlM{ODBibl2= NWTtVpk2TE2VTx?= MXzpcohq[mm2czDDbIsyKGGldHn2bZR6 M1P0cFI1OTF2MUK0
Calu6 NVjEPIg5U2mwYYPlJIF{e2G7 NY\6NmFKOzNyMDDuUS=> NF3s[YNFVVOR NEK2U|lqdmirYnn0d{BEcGtzIHHjeIl3cXS7 Ml\kNlQyOTRzMkS=
A549 NV;JWIpzTnWwY4Tpc44h[XO|YYm= MmT3glExKM7:TR?= NWriNGI1TE2VTx?= M2PtZYlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= M1;0elI1QTJ6MkC1
H1299 MWrGeY5kfGmxbjDhd5NigQ>? M2j2Z54yOCEQvF2= M3PsSGROW09? NUjzdlhJcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> NGTM[oMzPDl{OEKwOS=>
A549 MkjmSpVv[3Srb36gZZN{[Xl? NEHDZlB,OjBizszN M2LFNGROW09? MXvhZ5RqfmG2ZYOgSG5CKGSjbXHn[UB{\W6|b4Kgb4lv[XOncx?= M13ERVI1QTJ6MkC1
H1299 M33mfWZ2dmO2aX;uJIF{e2G7 NWnUcoVxhjJyIN88US=> MWnEUXNQ MmrmZYN1cX[jdHXzJGRPSSCmYX3h[4Uhe2Wwc3;yJItqdmG|ZYO= M1\IPFI1QTJ6MkC1
A549 M4\1RmFxd3C2b4Ppd{Bie3OjeR?= MljBglIxKM7:TR?= MXXEUXNQ MlTvbY5lfWOnczDhdI9xfG:|aYO= M13QN|I1QTJ6MkC1
H1299 MonhRZBweHSxc3nzJIF{e2G7 NFL0fYZ,OjBizszN MYjEUXNQ M1LVXolv\HWlZYOgZZBweHSxc3nz M37pNlI1QTJ6MkC1
A549 NGi2e29EgXSxeHnjbZR6KGG|c3H5 NG[w[oh,OjBizszN Mn;mSG1UVw>? NHnPV3NqdmS3Y3XzJIF2fG:yaHHnfS=> MoL3NlQ6Ojh{MEW=
H1299 MUDDfZRwgGmlaYT5JIF{e2G7 NGnw[ld,OjBizszN NX[wNop{TE2VTx?= MYjpcoR2[2W|IHH1eI9xcGGpeR?= MV[yOFkzQDJyNR?=
A549 Mm\ISpVv[3Srb36gZZN{[Xl? NFjqdGJ,OjBizszN NVz3e4VbTE2VTx?= M3HvTIlv[3KnYYPld{BLVktiYX7kJJA{QCCPQWDLJJBpd3OyaH;yfYxifGmxbh?= M4e3PVI1QTJ6MkC1
H1299 NVe0O3doTnWwY4Tpc44h[XO|YYm= MVv+NlAh|ryP NHHIVopFVVOR MkjRbY5kemWjc3XzJGpPUyCjbnSgdFM5KE2DUFugdIhwe3Cqb4L5cIF1cW:w NEfIW|EzPDl{OEKwOS=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-Chk1 / Chk1 / CDC25A ; 

PubMed: 29326282     


CHK1 inhibition was monitored by measuring levels of CHK1 p-S345 and CDC25A by western blots. Cells were treated with various concentrations of LY2603618 for 8 h. 

PARP / CF-PARP / p-CDC25C / p-CDK1 / p-CDK2 ; 

PubMed: 25458954     


BxPC-3 cells were treated with vehicle control, MK-1775 (MK), LY2603618 (LY) or MK-1775 plus LY2603618 for 48 h. Protein extracts were subjected to Western blotting and probed with anti-PARP, -p-CHK1, -CHK1, -p-CDC25C, -p-CDK1, -CDK1, -p-CDK2, -CDK2, -γH2AX, or -β-actin antibody. 

29326282 25458954
Growth inhibition assay
Cell viability; 

PubMed: 29326282     


MTT assay following CHK1 inhibition by LY2603618 in BC cells with higher RNF126 expression vs. BC cells with lower RNF126 expression. Cells were treated with various concentrations of LY2603618 for 72 h. n=3. (Two-way ANOVA, P(BT474 VS. MDA-MB-231)<0.001; P(BT474 VS. MDA-MB-468)<0.001; P(ZR751 VS. MDA-MB-231)<0.001; P(ZR751 VS. MDA-MB-468)<0.001).

29326282
In vivo In xenograft models, LY2603618 delays tumor growth when given in combination with pemetrexed. [3]

Protocol

Cell Research:

[4]

+ Expand
  • 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.


    (Only for Reference)

Solubility (25°C)

In vitro DMSO 13 mg/mL (29.79 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG400+0.5% Tween80+5% Propylene glycol
For best results, use promptly after mixing.
30mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 436.3
Formula

C18H22BrN5O3

CAS No. 911222-45-2
Storage powder
in solvent
Synonyms IC-83

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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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID