880487-62-7

880487-62-7 structure

Name: Phthalazinone pyrazole
Chemical Name: 4-[(5-Methyl-1H-pyrazol-3-yl)amino]-2-phenyl-1(2H)-phthalazinone
CAS Number: 880487-62-7
Molecular Formula: C₁₈H₁₅N₅O
Molecular Weight: 317.345
Catalog: Signaling Pathways Cell Cycle/DNA Damage Aurora Kinase
Create Date: 2016-05-26 23:41:07
Modify Date: 2024-01-08 18:41:42
Phthalazinone pyrazole is a potent, selective, and orally active inhibitor of Aurora-A kinase with an IC50 of 0.031 μM. Phthalazinone pyrazole can arrests mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells. Phthalazinone pyrazole suppresses the epithelial-mesenchymal transition (EMT) during the differentiation of hepatocyte-like cells (HLCs) from human embryonic stem cells[1][2].

Name	4-[(5-Methyl-1H-pyrazol-3-yl)amino]-2-phenyl-1(2H)-phthalazinone
Synonyms	4-[(5-Methyl-1H-pyrazol-3-yl)amino]-2-phenyl-1(2H)-phthalazinone 1(2H)-Phthalazinone, 4-[(5-methyl-1H-pyrazol-3-yl)amino]-2-phenyl- Phthalazinone Pyrazole

Description	Phthalazinone pyrazole is a potent, selective, and orally active inhibitor of Aurora-A kinase with an IC50 of 0.031 μM. Phthalazinone pyrazole can arrests mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells. Phthalazinone pyrazole suppresses the epithelial-mesenchymal transition (EMT) during the differentiation of hepatocyte-like cells (HLCs) from human embryonic stem cells[1][2].
Related Catalog	Signaling Pathways >> Epigenetics >> Aurora Kinase Research Areas >> Cancer Signaling Pathways >> Cell Cycle/DNA Damage >> Aurora Kinase
Target	Aurora-A:0.031 μM (IC50)
In Vitro	Phthalazinone pyrazole (1 and 10 μM; 30 hours) enhances the proliferative capacity of HLCs[2]. Phthalazinone pyrazole (1, 10, and 100 μM; 5 days) enhances hepatic morphological changes in differentiated HLCs without cytotoxicity[2]. Phthalazinone pyrazole (1 and 10 μM; 5 and 17 days) suppresses the EMT and induced maturation of HLCs through the inhibition of the AKT signaling pathway by the off target effect with concomitant upregulation of HNF4α rather than direct inhibition of Aurora-A. The result is confirmed by western blot and qPCR[2]. Cell Proliferation Assay[2] Cell Line: Hepatocyte-like cells (HLCs) Concentration: 1 and 10 μM Incubation Time: 30 hours Result: Enhanced the proliferative capacity of HLCs. Cell Cytotoxicity Assay[2] Cell Line: ES-HLCs, iPS-HLCs, Huh7 cells Concentration: 1, 10, and 100 μM Incubation Time: 5 days Result: Showed no cytotoxic effects on HLCs. Western Blot Analysis[2] Cell Line: HLCs Concentration: 1 and 10 μM Incubation Time: 5 and 17 days Result: Markedly inhibited the phosphorylation of AKT and activated GSK-3β, which in turn inhibited Snail expression and increased HNF4α. Phthalazinone pyrazole didn’t significantly reduce the phosphorylation of Aurora-A. RT-PCR[2] Cell Line: HLCs Concentration: 1 and 10 μM Incubation Time: 5 and 17 days Result: Markedly inhibited the phosphorylation of AKT mRNA and activated GSK-3β mRNA, which in turn inhibited Snail mRNA expression and increased HNF4α mRNA. Phthalazinone pyrazole didn’t significantly reduce the phosphorylation of Aurora-A mRNA.
References	[1]. Prime ME, et al. Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase. J Med Chem. 2011;54(1):312-319. [2]. Choi YJ, et al. Phthalazinone Pyrazole Enhances the Hepatic Functions of Human Embryonic Stem Cell-Derived Hepatocyte-Like Cells via Suppression of the Epithelial-Mesenchymal Transition. Stem Cell Rev Rep. 2018;14(3):438-450.

Density	1.4±0.1 g/cm3
Boiling Point	557.7±52.0 °C at 760 mmHg
Molecular Formula	C₁₈H₁₅N₅O
Molecular Weight	317.345
Flash Point	291.1±30.7 °C
Exact Mass	317.127655
PSA	78.83000
LogP	3.03
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.716

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