AMG 900 | CAS:945595-80-2

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Name:AMG 900; 
Cat. No. :CS-0485
CAS No. :945595-80-2
Formula:C28H21N7OS
M. Wt. : 503.58
Solubility:10 mM in DMSO

AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor with IC50 of 5 nM, 4 nM and 1 nM for Aurora A, B and C, respectively.IC50 & Target: IC50: 5 nM (Aurora A), 4 nM (Aurora B), 1 nM (Aurora C)[1]Ki: 3 nM (Aurora A), 2 nM (Aurora B), 1 nM (Aurora C)[1]In Vitro: AMG 900 inhibits the enzyme activity of all 3 aurora kinase family members with IC50 values of 5 nM or less. In HeLa cells, AMG 900 inhibits autophosphorylation of aurora-A and -B in a concentration-dependent manner. Treatment of HCT116 cells with 50 nM of AMG 900 for 48 hours resulted in polyploidy and suppresses the formation of colonies after cell replating. AMG 900 inhibits cell proliferation, with EC50 values ranging from 0.7 to 5.3 nM. Importantly, 4 of these AMG 900-sensitive cell lines (HCT-15, MES-SA-Dx5, 769P, and SNU449) are resistant to paclitaxel and other anticancer agents. AMG 900 inhibits p-histone H3 or induced polyploidy across all the cell lines tested irrespective of P-gp or BCRP status with uniform potency (IC50 or EC50 values ranging from 2 to 3 nM)[1].In Vivo: AMG 900 exhibits significant antitumor activity in all 9 xenograft models tested (50%-97% TGI compared with the vehicle-treated control group, P[1]. Treatment with AMG 900 at 15 mg/kg significantly inhibits p-Histone H3 in the G2M cell population in mouse bone marrow (upper panel) and cytokeratin positive COLO 205 tumor (lower panel) compared with vehicle-treated controls[2]. 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 h. AMG 900 is well-absorbed in fasted animals with an oral bioavailability of 31% to 107%. Food intake had an effect on rate (rats) or extent (dogs) of AMG 900 oral absorption[3].

Juan G, et al. AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues. J Transl Med. 2014 Nov 4;12:307. 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), 9846-9854. Huang L, et al. In vitro and in vivo pharmacokinetic characterizations of AMG 900, an orally bioavailable small molecule inhibitor of aurora kinases. Xenobiotica. 2011 May;41(5):400-8.