| Identification | Back Directory | [Name]
5-(5-(2-(3-aMinopropoxy)-6-Methoxyphenyl)-1H-pyrazol-3-ylaMino)pyrazine-2-carbonitrile hydrochloride | [CAS]
1234015-54-3 | [Synonyms]
LY2606368 2HCL
Prexasertib HCl
LY 2606368;LY-2606368
LY-2606368 (Prexasertib)
LY2606368 dihydrochloride
LY-2606368 dihydrochloride
Prexasertib HCl (LY2606368)
Prexasertib dihydrochloride
Prexasertib (LY2606368) 2HCl
LY 2606368;LY-2606368;PREXASERTIB DIHYDROCHLORIDE
5-(5-(2-(3-aMinopropoxy)-6-Methoxyphenyl)-1H-pyrazol-3-ylaMino)pyrazine-2-carbonitrile hydrochloride
5-(5-(2-(3-aMinopropoxy)-6-Methoxyphenyl)-1H-pyrazol-3-ylaMino)pyrazine-2-carbonitrile dihydrochloride | [Molecular Formula]
C18H21Cl2N7O2 | [MOL File]
1234015-54-3.mol | [Molecular Weight]
438.311 |
| Chemical Properties | Back Directory | [storage temp. ]
Inert atmosphere,Store in freezer, under -20°C | [solubility ]
DMSO:12.5(Max Conc. mg/mL);28.52(Max Conc. mM) | [form ]
Solid | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
Prexasertib HCl is a member of the serine/threonine protein kinase family and is the core protein of cell cycle checkpoints in DNA damage response (DDR). | [Uses]
Prexasertib dihydrochloride (LY2606368 dihydrochloride) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a Ki of 0.9 nM and an IC50 of <1 nM. Prexasertib dihydrochloride inhibits CHK2 (IC50=8 nM) and RSK1 (IC50=9 nM). Prexasertib dihydrochloride causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dihydrochloride shows potent anti-tumor activity[1][2]. | [Biological Activity]
Prexasertib HCl is an ATP-competitive inhibitor of CHK1 with a Ki value of 0.9 nM. In cell-free experiments, the IC50 values of it for CHK2 and RSK were 8 nM and 9 nM, respectively. | [in vivo]
Prexasertib dihydrochloride (LY2606368 dihydrochloride; 1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) causes growth inhibition in tumor xenografts[1].
?
Prexasertib dihydrochloride (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%).
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| 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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| [target]
| Target | Value | Chk1
(Cell-free assay) | 0.9 nM(Ki) | Chk2
(Cell-free assay) | 8 nM | < tr> RSK
(Cell-free assay) | 9 nM |
| [IC 50]
Chk1: 0.9 nM (Ki); Chk1: <1 nM (IC50); Chk2: 8 nM (IC50) | [storage]
Store at -20°C | [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 DOI:10.1158/1535-7163.MCT-14-1037
[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. PMID:28401005 |
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