| Identification | Back Directory | [Name]
AMG 900 | [CAS]
945595-80-2 | [Synonyms]
AMG 900
AMG-900;AMG900
AMG 900 USP/EP/BP
N-(4-((3-(2-Aminopyrimidin-4-yl)pyridin-2-yl)oxy)phenyl)-4-(4-methylthiophen-2-yl)phthalazin-1
N-[4-[[3-(2-Amino-4-pyrimidinyl)-2-pyridinyl]oxy]phenyl]-4-(4-methyl-2-thienyl)-1-phthalazinamine
1-Phthalazinamine, N-[4-[[3-(2-amino-4-pyrimidinyl)-2-pyridinyl]oxy]phenyl]-4-(4-methyl-2-thienyl)-
N-[4-[[3-(2-Amino-4-pyrimidinyl)-2-pyridinyl]oxy]phenyl]-4-(4-methyl-2-thienyl)-1-phthalazinamine AMG 900 | [Molecular Formula]
C28H21N7OS | [MDL Number]
MFCD18633194 | [MOL File]
945595-80-2.mol | [Molecular Weight]
503.59 |
| Chemical Properties | Back Directory | [Boiling point ]
778.7±70.0 °C(Predicted) | [density ]
1.380 | [storage temp. ]
Keep in dark place,Sealed in dry,2-8°C | [solubility ]
≥25.2 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH | [form ]
solid | [pka]
4.79±0.30(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
Three Aurora kinases, A-C, are involved in phosphorylation events that are critical for the completion of mitosis. Their expression is elevated in a variety of human cancers. AMG 900 is an orally bioavailable, selective Aurora kinase inhibitor with IC50 values of 5, 4, and 1 nM for Aurora A, B, and C, respectively.1 It is greater than 10-fold selective for Aurora kinases over p38α, TYK2, JNK2, Met, and Tie2 (IC50s = 53, 220, 520, 550, and 650 nM, respectively).1 At 2-3 nM, AMG 900 has been shown to inhibit the proliferation of 26 different tumor cell lines in vitro, including cell lines resistant to either the antimitotic agent paclitaxel (Item No. 10461) or to other Aurora kinase inhibitors.1 Furthermore, AMG 900 is reported to be broadly active in multiple xenograft models, including three multidrug-resistant xenograft models, representing five tumor types.1 | [Enzyme inhibitor]
This potent and highly selective mitotic protein kinase inhibitor (FW =
503.58 g/mol; CAS 945595-80-2; Solubility: 100 mg/mL DMSO), also
named N- (4- (3- (2-aminopyrimidin-4-yl) pyridin-2-yloxy) phenyl) -4- (4-
methylthiophen-2-yl) phthalazin-1-amine, targets Aurora A (IC50 = 5 nM),
Aurora B (IC50 = 4 nM), and Aurora C (IC50 = 1 nM) protein kinases, with
>10-fold selectivity versus p38α, Tyk2, JNK2, Met and Tie2. The
modal tumor cell response to AMG 900 treatment is aborted cell division
without prolonged mitotic arrest, ultimately resulting in cell death.
AMG 900 exhibits acceptable PK properties in preclinical species and is
predicted to have low clearance in humans. Male rats metabolize AMG
900 primarily through hydroxylation with subsequent sulfate conjugation
on the pyrimidinyl-pyridine side-chain, whereas female rats favor oxidation
on the thiophene ring's methyl group, which is then metabolized to a
carboxylic acid, attended by conjugation to an acyl glucuronide. At
low-nM concentrations, AMG 900, whether administered alone or in
combination with microtubule-targeting drugs (paclitaxel or ixabepilone),
may be an effective intervention strategy for the treatment of metastatic
breast cancer and provide potential therapeutic options for patients with
multidrug-resistant tumors. It is, in fact, also active against taxane-
resistant tumor cell lines. | [target]
Aurora A | [References]
1. payton, m., et al., preclinical evaluation of amg 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. cancer res, 2010. 70(23): p. 9846-54.2. geuns-meyer, s., et al., discovery of n-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4- (4-methylthiophen-2-yl)p hthalazin-1-amine (amg 900), a highly selective, orally bioavailable inhibitor of aurora kinases with activity against multidrug-resistant cancer cell lines. j med chem, 2015. 58(13): p. 5189-207. |
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| Company Name: |
NCE Biomedical Co.,Ltd.
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| Tel: |
4000-027-021 |24 +86-13986109188 | +86-15623472865 | +81-08033611988 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15748/0.htm |
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