Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate) 是一种选择性的，ATP 竞争性的第二代细胞周期检测点激酶 1 (CHK1) 抑制剂，Ki为 0.9 nM，IC50为<1 nm。prexasertib mesylate hydrate 抑制 CHK2 (IC50=8 nM) 和 RSK1 (IC50=9 nM)。Prexasertib Mesylate Hydrate 引起双链 DNA 断裂和复制突变，导致细胞凋亡 (apoptosis)。Prexasertib Mesylate Hydrate 显示有效的抗肿瘤活性。
| 生物活性 | Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate) is a selective, ATP-competitive second-generationcheckpoint kinase 1 (CHK1)inhibitor with aKiof 0.9 nM and anIC50of<1 nm. prexasertib mesylate hydrate inhibitsCHK2(IC50=8 nM) andRSK1(IC50=9 nM). Prexasertib Mesylate Hydrate causes double-stranded DNA breakage and replication catastrophe resulting inapoptosis. Prexasertib Mesylate Hydrate shows potent anti-tumor activity[1][2]. |
| IC50& Target | Chk1 0.9 nM (Ki) | Chk1 <1 nM (IC50) | Chk2 8 nM (IC50) |
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体外研究
(In Vitro) | Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate) inhibits MELK (IC50=38 nM), SIK (IC50=42 nM), BRSK2 (IC50=48 nM), ARK5 (IC50=64 nM). LY2606368 requires CDC25A and CDK2 to cause DNA damage[1].
Prexasertib Mesylate Hydrate (33, 100 nM; for 7 hours) results in DNA damage during S-phase in HeLa cells[1].
Prexasertib Mesylate Hydrate (8-250 nM; pre-treated for 15 minutes) inhibits CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) in HT-29 cells[1].
Prexasertib Mesylate Hydrate (4 nM; 24 hours) results in a large shift in cell-cycle populations from G1 and G2-M to S-phase with an accompanied induction of H2AX phosphorylation in U-2 OS cells[1].
Prexasertib Mesylate Hydrate (33 nM; for 12 hours) causes chromosomal fragmentation in HeLa cells. Prexasertib Mesylate Hydrate (100 nM; 0.5 to 9 hours) induces replication stress and depletes the pool of available RPA2 for binding to DNA[1].
Cell Cycle Analysis[1] | Cell Line: | HeLa cells | | Concentration: | 33, 100 nM | | Incubation Time: | For 7 hours | | Result: | Had an IC50of 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 Line: | HT-29 cells | | Concentration: | 8, 16, 31, 63, 125, 250 nM | | Incubation Time: | Pre-treated for 15 minutes | | Result: | Inhibited CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) (IC50of less than 31 nM) in HT-29 cells. |
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体内研究
(In Vivo) | Prexasertib Mesylate Hydrate (LY2606368 Mesylate Hydrate; 1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) causes growth inhibition in tumor xenografts[1].
Prexasertib Mesylate Hydrate (15 mg/kg; SC) causes CHK1 inhibition in the blood and the phosphorylation of both H2AX (S139) and RPA2 (S4/S8)[1].
| Animal Model: | Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells[1] | | Dosage: | 1, 3.3, or 10 mg/kg | | Administration: | SC; twice daily for 3 days, rest 4 days; for three cycles | | Result: | Caused statistically significant tumor growth inhibition (up to 72.3%). |
| Animal Model: | Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells[1] | | Dosage: | 15 mg/kg (Pharmacokinetic Analysis) | | Administration: | SC (200 μL) | | Result: | CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures.
Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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