Rabusertib (LY2603618)

Catalog No.S2626 Batch:S262606

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Technical Data

Formula

C18H22BrN5O3
Molecular Weight 436.3 CAS No. 911222-45-2
Solubility (25°C)* In vitro DMSO 13 mg/mL (29.79 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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]
In vivo

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

Protocol (from reference)

Cell Assay:

[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.
Animal Study:

[5]
  • Animal Models

    Male Wistar rats

  • Dosages

    50 mg/kg

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by J Hematol Oncol, 2014, 7, 53]

Data from [Data independently produced by Cancer Lett, 2014, 10.1016/j.canlet.2014.10.015]

Data from [Data independently produced by BMC Cancer, 2014, 14, 483]

, , Customer W, F. Z

Selleck's Rabusertib (LY2603618) has been cited by 88 publications

mTORC1 activity oscillates throughout the cell cycle promoting mitotic entry and differentially influencing autophagy induction [ bioRxiv, 2024, 2024.02.06.579216] PubMed: 38370755
Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1 [ Nat Commun, 2023, 14(1):6088] PubMed: 37773176
An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress [ Nat Commun, 2023, 14(1):4991] PubMed: 37591859
An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress [ Nat Commun, 2023, 14(1):4991] PubMed: 37591859
Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage response [ EMBO Mol Med, 2023, e16431.] PubMed: 37485814
Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects [ J Immunother Cancer, 2023, 11(2)e004871] PubMed: 36759012
VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU [ Cell Death Dis, 2023, 14(2):114] PubMed: 36781846
Arginine shortage induces replication stress and confers genotoxic resistance by inhibiting histone H4 translation and promoting PCNA ubiquitination [ Cell Rep, 2023, 42(4):112296] PubMed: 36961817
Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment [ Cell Rep, 2023, 42(9):113098] PubMed: 37714156
BRD7 suppresses tumor chemosensitivity to CHK1 inhibitors by inhibiting USP1-mediated deubiquitination of CHK1 [ Cell Death Discov, 2023, 9(1):313] PubMed: 37626049

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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