Product Name: AMG 900
Synonyms: AMG
900;N-[4-[[3-(2-Amino-4-pyrimidinyl)-2-pyridinyl]oxy]phenyl]-4-(4-methyl-2-thienyl)-1-phthalazinamine;N-[4-[[3-(2-Amino-4-pyrimidinyl)-2-pyridinyl]oxy]phenyl]-4-(4-methyl-2-thienyl)-1-phthalazinamine
AMG 900
CAS: 945595-80-2
MF: C28H21N7OS
MW: 503.58
Product Categories: Inhibitor
density 1.380
Appearance : White powders
Purity : 99%
Package : 1kg/foil bag
Usage: AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor for Aurora A/B/C with IC50 of 5 nM/4 nM /1 nM. It is >10-fold selective for Aurora kinases than p38α, Tyk2, JNK2, Met
and Tie2.
In vitro:
AMG 900 is a novel class of ATP-competitive phthalazinamine small molecule inhibitors of aurora kinases. In HeLa cells, AMG 900 inhibits autophosphorylation of aurora-A and -B as well as
phosphorylation of histone H3 on Ser, a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG 900 treatment is aborted cell division without a prolonged mitotic
arrest, which ultimately results in cell death. AMG 900 inhibits the proliferation of 26 tumor cell lines, including cell lines resistant to the antimitotic drug paclitaxel and to other aurora
kinase inhibitors (AZD1152, MK-0457, and PHA-739358), at low nanomolar concentrations (about 2- 3 nM). Furthermore, AMG 900 is active in an AZD1152-resistant HCT116 variant cell line that harbors
an aurora-B mutation (W221L).
In vivo:
Oral administration of AMG 900 blocks the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. AMG 900 is broadly active in
multiple xenograft models, including 3 multidrugresistant xenograft models, representing 5 tumor types. AMG 900 exhibits a low-to-moderate clearance and a small volume of distribution. Its terminal
elimination half-life ranged from 0.6 to 2.4 hours. AMG 900 is well-absorbed in fasted animals with an oral bioavailability of 31% to 107%. Food intake has an effect on rate (rats) or extent (dogs)
of AMG 900 oral absorption. The clearance and volume of distribution at steady state in humans are predicted to be 27.3 mL/h/kg and 93.9 mL/kg, respectively. AMG 900 exhibits acceptable PK
properties in preclinical species and is predicted to have low clearance in humans.
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