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LY2603618 (Synonyms: IC-83, Rabusertib)

Catalog No.GC15741

LY2603618 (LY2603618) is a potent and selective inhibitor of Chk1 with an IC50 of 7 nM.

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LY2603618 Chemical Structure

Cas No.: 911222-45-2

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10mM (in 1mL DMSO)
$90.00
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5mg
$66.00
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10mg
$100.00
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50mg
$309.00
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200mg
$713.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

HeLa cervical cancer cells, Calu-6 non-small cell lung cancer cells, HT29 and HCT-116 colon cancer cells

Preparation method

The solubility of this compound in DMSO is >21.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1250 nM, 2500 nM, 24 h

Applications

Treatment with 1250 nM LY2603618 resulted in a clear decrease in the G1 population and an increase in late S-phase cells. Cells treated with 5000 nM LY2603618 were predominantly found in the S-phase peak with a DNA content intermediate between 2 and 4N. LY2603618 induced DNA damage and arrested DNA synthesis while increasing the number of cells expressing an early marker of mitosis. LY2603618 treated cells lacked normal mitotic cells. An increased proportion of LY2603618 treated cells stained for pH3(S10) and were arrested in an abnormal prometaphase relative to the control cells. LY2603618 increased the potency of gemcitabine in p53-mutant HT-29 cells, but not in p53 WT HCT-116 cells

Animal experiment [1]:

Animal models

Female Harlan athymic nude mice bearing Calu-6 xenografts

Dosage form

Oral administration, 200 mg/kg

Application

LY2603618 effectively inhibited the activation of Chk1 but not ATR by gemcitabine in Calu-6 tumor xenografts.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. King C, Diaz H, Barnard D, et al. Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor[J]. Investigational new drugs, 2014, 32(2): 213-226.

Background

LY2603618 is a novel small molecular checkpoint kinase 1 (Chk1) inhibitor that has direct anti-tumour effect [1], as well as desensitizing tumour cell against DNA-damaging chemotherapy treatment [2].

Checkpoint kinase 1 (Chk1) is a type of kinase that coordinates damaged-DNA repair [1]. Some tumour cells have been found to possess over-regulated populations of Chk1 that desensitize the cell from DNA-targeting chemotherapy, promoting tumour proliferation [3].

LY2603618 inhibits Chk1 by competing with ATP molecules [2]. In A549 and H1299 non-small cancer cell lines, lethal concentration of LY2603618 (10 µM) not only resulted in cell proliferation arrest (increase population of cell at G2/M phase from 13% to 38%) but also directly DNA damage, the latter of which was indicated by the increasing occurrence of H2AX phosphorylation[1].

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].

References:
[1].  Wang F Z, Fei H R, Cui, Y J et al. The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Apoptosis, 2014,19:1389-1398.
[2].  King C, Diaz H, Barnard D et al.Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs, 2014, 32: 213-26.
[3].  Zhang Y. & Hunter T. Roles of Chk1 in cell biology and cancer therapy. Int J Cancer, 2014. 134: 1013-23.

Chemical Properties

Cas No. 911222-45-2 SDF
Synonyms IC-83, Rabusertib
Chemical Name 1-[5-bromo-4-methyl-2-[[(2S)-morpholin-2-yl]methoxy]phenyl]-3-(5-methylpyrazin-2-yl)urea
Canonical SMILES CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OCC3CNCCO3
Formula C18H22BrN5O3 M.Wt 436.3
Solubility ≥ 43.6mg/mL in DMSO with gentle warming Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.292 mL 11.46 mL 22.92 mL
5 mM 0.4584 mL 2.292 mL 4.584 mL
10 mM 0.2292 mL 1.146 mL 2.292 mL
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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.

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Reviews

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Average Rating: 5 ★★★★★ (Based on Reviews and 16 reference(s) in Google Scholar.)

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