| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| Targets |
Chk1 0.9 nM (Ki) Chk1 <1 nM (IC50) Chk2 8 nM (IC50)
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| ln Vitro |
Prexasertib dimesylate (LY2606368 dimesylate) suppresses BRSK2 (IC50=48 nM), ARK5 (IC50=64 nM), SIK (IC50=42 nM), and MELK (IC50=38 nM). DNA damage caused by prexasertib dimesylate requires the presence of CDK2 and CDC25A[1]. In HeLa cells, prexasertib dimesylate (33, 100 nM) causes DNA damage during the S-phase[1]. In HT-29 cells, prexasertib dimesylate (8-250 nM; pre-treated for 15 minutes) suppresses the autophosphorylation of CHK1 (S296 ) and CHK2 (S516). In U-2 OS cells, prexasertib dimesylate (4 nM; 24 hours) induces H2AX phosphorylation and causes a significant shift in cell cycle populations from G1 and G2-M to S-phase[1]. In HeLa cells, proxasertib dimesylate (33 nM) for 12 hours fragments the chromosomes. Prexasertib dimesylate (100 nM; 0.5 to 9 hours) reduces the amount of RPA2 that is available to bind to DNA and causes replication stress[1].
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| ln Vivo |
Tumor xenografts grow less rapidly when treated with prexasertib dimesylate (LY2606368 dimesylate; 1–10 mg/kg; SC; twice daily for three days, rest four days)[1]. Tumor xenografts treated with prexasertib dimesylate (15 mg/kg; SC) exhibit growth inhibition[1]. Inhibition of CHK1 in blood and phosphorylation of RPA2 (S4/S8) and H2AX (S139)[1].
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| Cell Assay |
Cell Cycle Analysis[1]
Cell Types: HeLa cells Tested Concentrations: 33, 100 nM Incubation Duration: For 7 hrs (hours) Experimental Results: Had an IC50 of 37 nM and resulted in the G2-M population received DNA damage during S-phase but continued to progress through the cell cycle into an early mitosis. Western Blot Analysis[1] Cell Types: HT- 29 cells Tested Concentrations: 8, 16, 31, 63, 125, 250 nM Incubation Duration: Pre-treated for 15 minutes Experimental Results: Inhibited CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) (IC50 of less than 31 nM) in HT- 29 cells. |
| Animal Protocol |
Animal/Disease Models: Female CD-1 nu -/nu- mice (26-28 g) with Calu-6 cells[1]
Doses: 1, 3.3, or 10 mg/kg Route of Administration: SC; twice (two times) daily for 3 days, rest 4 days; for three cycles Experimental Results: Caused statistically significant tumor growth inhibition (up to 72.3%). Animal/Disease Models: Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells[1] Doses: 15 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: SC (200 μL) Experimental Results: CHK1 was 7 ng/mL at 12 hrs (hours) and 3 ng/mL by 24 hrs (hours) in plasma exposures. Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hrs (hours), showing the rapid occurrence of DNA damage. |
| References |
[1]. King C, et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-1
[2]. Yin Y, et al. Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer. Am J Cancer Res. 2017 Mar 1;7(3):473-483. |
| Molecular Formula |
C20H27N7O8S2
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|---|---|
| Molecular Weight |
557.60
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| CAS # |
1234015-58-7
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| Related CAS # |
Prexasertib;1234015-52-1;Prexasertib dihydrochloride;1234015-54-3;Prexasertib Mesylate Hydrate;1234015-57-6;Prexasertib mesylate;1234015-55-4
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| SMILES |
S(C)(=O)(=O)O.S(C)(=O)(=O)O.O(CCCN)C1C=CC=C(C=1C1=CC(NC2C=NC(C#N)=CN=2)=NN1)OC
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (179.34 mM)
H2O : 50 mg/mL (89.67 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.5 mg/mL (6.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.5 mg/mL (6.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7934 mL | 8.9670 mL | 17.9340 mL | |
| 5 mM | 0.3587 mL | 1.7934 mL | 3.5868 mL | |
| 10 mM | 0.1793 mL | 0.8967 mL | 1.7934 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.
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