tcsc0485 AMG 900

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<0.005, P<0.0005). Importantly, AMG 900 is active in the MES-SA-Dx5 (84% TGI, P<0.0001) and NCI-H460-PTX (66% TGI, P<0.0001) xenograft models that are resistant to either Docetaxel or Paclitaxel administered at their respective maximum tolerated doses. AMG 900 inhibits the activity of aurora-B in HCT116 tumors and suppresses the growth of multiple xenografts that represent diverse tumor types^[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].