WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 204370
Description: AMG 900 is a small-molecule inhibitor of Aurora kinases A, B and C with potential antineoplastic activity. Aurora kinase inhibitor AMG 900 selectively binds to and inhibits the activities of Aurora kinases A, B and C, which may result in inhibition of cellular division and proliferation in tumor cells that overexpress these kinases. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis and are overexpressed by a wide variety of cancer cell types.
MedKoo Cat#: 204370
Chemical Formula: C28H21N7OS
Exact Mass: 503.15283
Molecular Weight: 503.57764
Elemental Analysis: C, 66.78; H, 4.20; N, 19.47; O, 3.18; S, 6.37
Synonym: AMG900; AMG-900; AMG 900.
IUPAC/Chemical Name: N-(4-((3-(2-aminopyrimidin-4-yl)pyridin-2-yl)oxy)phenyl)-4-(4-methylthiophen-2-yl)phthalazin-1-amine.
InChi Key: IVUGFMLRJOCGAS-UHFFFAOYSA-N
InChi Code: InChI=1S/C28H21N7OS/c1-17-15-24(37-16-17)25-20-5-2-3-6-21(20)26(35-34-25)32-18-8-10-19(11-9-18)36-27-22(7-4-13-30-27)23-12-14-31-28(29)33-23/h2-16H,1H3,(H,32,35)(H2,29,31,33)
SMILES Code: CC1=CSC(C2=NN=C(NC3=CC=C(OC4=NC=CC=C4C5=NC(N)=NC=C5)C=C3)C6=C2C=CC=C6)=C1
MG 900 is an orally bioavailable, potent, and highly selective pan-aurora kinase inhibitor that is active in taxane-resistant tumor cell lines. In tumor cells, AMG 900 inhibited autophosphorylation of aurora-A and -B as well as phosphorylation of histone H3 on Ser10, a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG 900 treatment was aborted cell division without a prolonged mitotic arrest, which ultimately resulted in cell death. AMG 900 inhibited 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. Furthermore, AMG 900 was active in an AZD1152-resistant HCT116 variant cell line that harbors an aurora-B mutation (W221L). Oral administration of AMG 900 blocked the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. Importantly, AMG 900 was broadly active in multiple xenograft models, including 3 multidrug-resistant xenograft models, representing 5 tumor types. AMG 900 has entered clinical evaluation in adult patients with advanced cancers and has the potential to treat tumors refractory to anticancer drugs such as the taxanes. (Source: Cancer Res; 70(23); 9846Â–54.)
1: Waldon D, Berry L, Lin MH, Schenkel L, Hollis LS, Zhao Z. Gender Effects on Rat Metabolism of AMG 900, an Orally Available Small Molecule Aurora Kinase Inhibitor. Drug Metab Lett. 2011 Oct 21. [Epub ahead of print] PubMed PMID: 22022868.
2: Huang L, Be X, Berry L, Moore E, Janosky B, Wells M, Pan WJ, Zhao Z, Lin MH. 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. Epub 2011 Feb 4. PubMed PMID: 21294625.
3: Payton M, Bush TL, Chung G, Ziegler B, Eden P, McElroy P, Ross S, Cee VJ, Deak HL, Hodous BL, Nguyen HN, Olivieri PR, Romero K, Schenkel LB, Bak A, Stanton M, Dussault I, Patel VF, Geuns-Meyer S, Radinsky R, Kendall RL. 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 Dec 1;70(23):9846-54. Epub 2010 Oct 8. PubMed PMID: 20935223.