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Purity: ≥98%
Prexasertib 2HCl (also known as LY2606368) is the dihydrochloride 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, respectively. The 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 establishes 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 works by inhibiting CHK1, which raises CDC25A activation of CDK2, increasing the number of replication forks while decreasing their stability. TUNEL and pH2AX-positive double-stranded DNA breaks quickly manifest in the S-phase cell population following Prexasertib treatment. Ex vivo tumor models demonstrate comparable responses to ixasertib, including marked inhibition of tumor growth. In conclusion, Prexasertib is a strong representative of a brand-new class of cancer treatment medications that works by causing a replication failure.
| Targets |
Chk1 (Ki = 0.9 nM); Chk1 (IC50 <1 nM); Chk2 (IC50 = 8 nM)
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| ln Vitro |
Prexasertib (also know LY2606368) 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, respectively. The 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 establishes DNA damage checkpoints in the cell cycle, CHK1 inhibitors are currently being studied as chemopotentiating agents. When taken by itself, prexasertib breaks double-stranded DNA and eliminates the DNA damage checkpoints' defenses. Prexasertib works by inhibiting CHK1, which raises CDC25A activation of CDK2, increasing the number of replication forks while decreasing their stability. TUNEL and pH2AX-positive double-stranded DNA breaks quickly manifest in the S-phase cell population following Prexasertib treatment. Ex vivo tumor models demonstrate comparable responses to ixasertib, including marked inhibition of tumor growth. In summary, Prexasertib is a powerful example of a new class of cancer treatment medications that works by causing a replication catastrophe.
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| ln Vivo |
Prexasertib (LY2606368), when used both alone and in conjunction with other agents, inhibited the growth of tumors in cancer xenografts. LY2606368 was found to suppress the growth of primary tumors and significantly lower the incidence of metastases and ascites accumulation in an orthotopic SKOV3 ovarian cancer model. Additionally, LY2606368 showed promise in an orthotopic pancreatic cancer model based on SW1990, leading to a 92% reduction in the growth of the primary tumor and the removal of metastases to the intestine, spleen, and lymph node.
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| 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.
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| Cell Assay |
On T25 flasks, HeLa cells were plated, and they were given 24 hours to heal. The final concentrations of 33 or 100 nmol/L were then obtained by adding LY2606368. In certain studies, the drug treatment included 20μmol/L Z-VAD-FMK. After the 12-hour treatment, 1 μg/mL of colchicine was added during the final two hours of treatment. Using the methodology of Bayani and Squire, nuclei were fixed for metaphase spreads. Chromosome spreads were done. A 12-μL volume of cell suspension in a 3:1 methanol/acetic acid fixative was dropped onto coverslips or dry glass slides from a height of 3 cm. After that, the slides were heated for 45 seconds on a metal block set at 43°C. After that, they were taken out to finish drying at room temperature. Using DAPI, coverslips were adhered to slides using Vectashield Hard Set mounting medium. A Leica DMR fluorescent microscope was used to examine the slides, and a SPOT RT3 Slider camera was used to take pictures.
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| Animal Protocol |
Female CD-1 nu-/nu- mice
15 mg/kg s.c. |
| References |
| Molecular Formula |
C₁₈H₂₁CL₂N₇O₂
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| Molecular Weight |
438.31
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| Exact Mass |
437.1133783
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| Elemental Analysis |
C, 49.33; H, 4.83; Cl, 16.18; N, 22.37; O, 7.30
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| CAS # |
1234015-54-3
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| Related CAS # |
Prexasertib;1234015-52-1;Prexasertib dimesylate;1234015-58-7;Prexasertib Mesylate Hydrate;1234015-57-6;Prexasertib mesylate;1234015-55-4
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| Appearance |
Solid powder
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| SMILES |
COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N.Cl.Cl
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| InChi Key |
KMEIPKXRCJTZBZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19N7O2.2ClH/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;;/h2,4-5,8,10-11H,3,6-7,19H2,1H3,(H2,22,23,24,25);2*1H
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| Chemical Name |
5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]pyrazine-2-carbonitrile;dihydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
5%DMSO+40%PEG300+5%Tween80+50%ddH2O: 0.5mg/ml (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2815 mL | 11.4075 mL | 22.8149 mL | |
| 5 mM | 0.4563 mL | 2.2815 mL | 4.5630 mL | |
| 10 mM | 0.2281 mL | 1.1407 mL | 2.2815 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.
Calculation results
Working concentration： mg/mL；
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.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Exposure to LY2606368 results in DNA damage during S-phase.Mol Cancer Ther.2015 Sep;14(9):2004-13. |
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 The DNA damage effects of LY2606368 are dependent upon CDC25A and CDK2.
LY2606368 causes chromosomal fragmentation.Mol Cancer Ther.2015 Sep;14(9):2004-13. |
LY2606368 causes DNA damage and growth inhibition in tumor xenografts.Mol Cancer Ther.2015 Sep;14(9):2004-13. |
 LY2606368 induces replication stress and depletes the pool of available RPA2 for binding to DNA.Mol Cancer Ther.2015 Sep;14(9):2004-13. |
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 Chk1 inhibitor LY2606368 can induce DNA damage and apoptosis, and can suppress cell proliferation in gastric cancer cells.
LY2606368 can sensitize the anticancer effect of PARP inhibitor BMN673 in gastric cancer cells.Am J Cancer Res.2017 Mar 1;7(3):473-483. |
 Chk1 inhibitor LY2606368 can suppress HR repair capacity.
LY2606368 and BMN673 combination has synergistic anticancer effect in gastric cancer PDX model.Am J Cancer Res.2017 Mar 1;7(3):473-483. |
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