Prexasertib mesylate hydrate (LY 2606368)

Alias: LY-2606368; LY 2606368; LY2606368; Prexasertib
Cat No.:V0081 Purity: =99.47%
Prexasertib mesylate hydrate (also known as LY2606368 mesylate hydrate) is the hydrated mesylate salt of Prexasertib with potential anticancer activity.
Prexasertib mesylate hydrate (LY 2606368) Chemical Structure CAS No.: 1234015-57-6
Product category: CDK
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of Prexasertib mesylate hydrate (LY 2606368):

  • Prexasertib (LY2606368)
  • Prexasertib 2HCl (LY-2606368)
  • Prexasertib dimesylate (LY2606368 dimesylate)
  • Prexasertib mesylate (LY-2606368 mesylate)
Official Supplier of:
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Top Publications Citing lnvivochem Products
InvivoChem's Prexasertib mesylate hydrate (LY 2606368) has been cited by 1 publication
Purity & Quality Control Documentation

Purity: =99.47%

Product Description

Prexasertib mesylate hydrate (also known as LY2606368 mesylate hydrate) is the hydrated mesylate salt of Prexasertib with potential anticancer activity. It is a novel, potent, selective and ATP competitive inhibitor of the protein kinase CHK1 (checkpoint kinase 1) with IC50 values of less than 1 nM for CHK1 and 8 nM for CHK2. A multifunctional protein kinase, CHK1 is essential for the regulation of the number of active replication forks in cells as well as the response of the cells to damage to DNA. Because CHK1 is involved in establishing DNA damage checkpoints in the cell cycle, CHK1 inhibitors are currently being studied as potential chemopotentiating agents. When taken by itself, prexasertib breaks double-stranded DNA and eliminates the DNA damage checkpoints' defenses. Prexasertib's action is reliant on CHK1 inhibition and the ensuing rise in CDC25A activation of CDK2, which raises the quantity of replication forks while decreasing their stability. Prexasertib treatment causes TUNEL and pH2AX-positive double-stranded DNA breaks to rapidly manifest in the S-phase cell population. Prexasertib significantly inhibits tumor growth in xenograft tumor models with comparable efficacy. To sum up, Prexasertib is a powerful example of a new class of cancer treatment medications that works by causing a replication catastrophe.

Biological Activity I Assay Protocols (From Reference)
Targets
Chk1 (Ki = 0.9 nM); Chk1 (IC50 <1 nM); Chk2 (IC50 = 8 nM)
ln Vitro
Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate) inhibits ARK5 (IC50=64 nM), BRSK2 (IC50=48 nM), SIK (IC50=42 nM), and MELK (IC50=38 nM). DNA deterioration caused by LY2606368 requires both CDK2 and CDC25A[1].
Prexasertib Mesylate Hydrate (8-250 nM; pre-treated for 15 minutes) causes damage to DNA during the S-phase in HT-29 cells[1].
Prexasertib Mesylate Hydrate (4 nM; 24 hours) causes a significant change in cell cycle populations from G1 and G2-M to S-phase, along with an increase in H2AX phosphorylation[1].
Prexasertib Mesylate Hydrate (33 nM; for 12 hours) causes the fragmentation of chromosomes in HeLa cells. Replication stress is induced by prexasertib Mesylate Hydrate (100 nM; 0.5 to 9 hours), which also reduces the amount of RPA2 that is available for DNA binding[1].
ln Vivo
Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate; 1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) inhibits the growth of tumor xenografts[1].
Prexasertib Mesylate Hydrate (15 mg/kg; SC) phosphorylates RPA2 (S4/S8) and H2AX (S139), inhibiting CHK1 in the blood[1].
Enzyme Assay
Prexasertib (LY2606368) inhibits CHK1 and CHK2 with IC50 values less than 1 nM and 8 nM, respectively, with a strong and specific potency. For CHK1 activity via serine 296 autophosphorylation, LY2606368 has an EC50 of 1 nM, and for HT-29 CHK2 autophosphorylation, it is <31 nM (S516). With an EC50 of 9 nM, LY2606368 potently inhibits the G2-M checkpoint that doxorubicin has activated in p53-deficient HeLa cells. Still, 100 nM Instead of weakly inhibiting PMA-stimulated RSK, LY2606368 slightly increases the phosphorylation of S6 on serines 235/236. LY2606368 exhibits broad antiproliferative activity against U-2 OS, Calu-6, HT-29, HeLa, and NCI-H460 cell lines, exhibiting IC50 values of 3 nM, 3 nM, 10 nM, 37 nM, and 68 nM, respectively. Induction of H2AX phosphorylation and a significant shift in cell-cycle populations from G1 and G2-M to S-phase are both brought about by LY2606368 (4 nM) in U-2 OS cells. The anti-proliferative properties of AGS and MKN1 cells are demonstrated by LY2606368 (25 μM). HR repair capacity in DR-GFP cells is inhibited by LY2606368 (20 nM). When combined with the PARP inhibitor BMN673, LY2606368 (5 nM) exhibits synergistic anticancer effects in gastric cancer cells.
Cell Assay
The MTS Cell Proliferation Colorimetric Assay Kit measures the anticancer effects of BMN673 and LY2606368, the proliferation inhibition effect of CHK1 ablation, and IR sensitivity. After seeding cells into 96-well cell culture plates, each well is treated according to the experiment conditions specified. After two hours of incubation, the cell viability of each well is measured using a microplate reader set to detect wavelengths of 490 nM.
Animal Protocol
Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells[1]
1, 3.3, or 10 mg/kg
SC; twice daily for 3 days, rest 4 days; for three cycles
References

[1]. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-1.

[2]. Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer. Am J Cancer Res. 2017 Mar 1;7(3):473-483.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C19H25N7O6S
Molecular Weight
479.51
Exact Mass
479.15870272
Elemental Analysis
C, 47.59; H, 5.26; N, 20.45; O, 20.02; S, 6.69
CAS #
1234015-57-6
Appearance
Solid powder
SMILES
COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N.CS(=O)(=O)O.O
InChi Key
LCYWXOLNJNHLGN-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H19N7O2.CH4O3S.H2O/c1-26-14-4-2-5-15(27-7-3-6-19)18(14)13-8-16(25-24-13)23-17-11-21-12(9-20)10-22-17;1-5(2,3)4;/h2,4-5,8,10-11H,3,6-7,19H2,1H3,(H2,22,23,24,25);1H3,(H,2,3,4);1H2
Chemical Name
5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]pyrazine-2-carbonitrile;methanesulfonic acid;hydrate
Synonyms
LY-2606368; LY 2606368; LY2606368; Prexasertib
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ≥ 60 mg/mL
Water: < 1mg/mL
Ethanol: < 1mg/mL
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.0855 mL 10.4273 mL 20.8546 mL
5 mM 0.4171 mL 2.0855 mL 4.1709 mL
10 mM 0.2085 mL 1.0427 mL 2.0855 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

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Biological Data
  • Prexasertib mesylate hydrate


    Exposure to LY2606368 results in DNA damage during S-phase.2015 Sep;14(9):2004-13.

  • Prexasertib mesylate hydrate


    The DNA damage effects of LY2606368 are dependent upon CDC25A and CDK2.


    Prexasertib mesylate hydrate

    LY2606368 causes chromosomal fragmentation.2015 Sep;14(9):2004-13.


  • Prexasertib mesylate hydrate

    LY2606368 causes DNA damage and growth inhibition in tumor xenografts.2015 Sep;14(9):2004-13.

  • Prexasertib mesylate hydrate


    LY2606368 induces replication stress and depletes the pool of available RPA2 for binding to DNA.2015 Sep;14(9):2004-13.

  • Prexasertib mesylate hydrate


    Chk1 inhibitor LY2606368 can induce DNA damage and apoptosis, and can suppress cell proliferation in gastric cancer cells.


    Prexasertib mesylate hydrate

    LY2606368 can sensitize the anticancer effect of PARP inhibitor BMN673 in gastric cancer cells.2017 Mar 1;7(3):473-483.

  • Prexasertib mesylate hydrateChk1 inhibitor LY2606368 can suppress HR repair capacity.



    Prexasertib mesylate hydrate

    LY2606368 and BMN673 combination has synergistic anticancer effect in gastric cancer PDX model.2017 Mar 1;7(3):473-483.

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