Description
AMG 925 is a dual inhibitor of FMS-related tyrosine kinase 3 (FLT3) and cyclin-dependent kinase 4 (Cdk4; IC
50s = 1 and 3 nM, respectively). It is selective for FLT3 and Cdk4 over Cdk1 (IC
50 = 2.22 μM). AMG 925 also binds to FLT3
ITD, FLT3
D835Y, FLT3
D835H, FLT3
K663Q, and FLT3
N841I (K
ds = 1-4 nM). It inhibits proliferation of MOLM-13, COLO 205, and U937 cancer cells (IC
50s = 19, 55, and 52 nM, respectively). AMG 925 (50, 75, and 150 mg/kg) reduces intratumor levels of pSTAT5 and pRb and inhibits tumor growth in a MOLM-13 acute myeloid leukemia (AML) mouse xenograft model.
Uses
AMG 925 is a FLT3 and CDK4 Dual Kinase Inhibitor with Preferential Affinity for the Activated State of FLT3.
Definition
ChEBI: AMG-925 is an organic heterotricyclic compound that is 9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidine which is substituted by a [6-(hydroxyacetyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl]nitrilo group at position 2 and by a trans-4-methylcyclohexyl group at position 9. It is a FLT3 and CDK4 dual kinase inhibitor that has antineoplastic activity. Currently under clinical investigation in patients with relapsed or refractory acute myeloid leukemia (AML). It has a role as an antineoplastic agent, an apoptosis inducer, an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor and an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor. It is a secondary amino compound, a tertiary amino compound, a naphthyridine derivative, a primary alpha-hydroxy ketone and an organic heterotricyclic compound.
References
[1] keegan k, li c, li z, ma j, ragains m, coberly s, hollenback d, eksterowicz j, liang l, weidner m, huard j, wang x, alba g, orf j, lo mc, zhao s, ngo r, chen a, liu l, carlson t, quéva c, mcgee lr, medina j, kamb a, wickramasinghe d, dai k. preclinical evaluation of amg 925, a flt3/cdk4 dual kinase inhibitor for treating acute myeloid leukemia. mol cancer ther. 2014 apr;13(4):880-9.
