N2-[2-Methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-1,3,5-triazine-2,4-diamine

Description

ASP3026 is an ATP-competitive, second-generation ALK inhibitor (IC₅₀ = 3.5 nM) that also inhibits ROS (IC₅₀ = 8.9 nM) and ACK (IC₅₀ = 5.8 nM). It inhibits neuroblastoma-activating ALK mutants F1174L (IC₅₀ = 10 nM) and R1275Q (IC₅₀ = 5.4 nM) and demonstrates antitumor activity in xenograft mouse models. ASP3026 has been shown to overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK-positive solid tumors.

Uses

ASP3026 is a novel and selective anaplastic lymphoma kinase (ALK) inhibitor that shows potent anti-tumor activities. ASP3026 also shows potential efficacy for non-small cell lung cancer (NSCLC) and is expected to improve the therapeutic outcomes of patients with cancer with ALK abnormality. Potent ALK inhibitor.

Definition

ChEBI: ASP-3026 is a member of the class of diamino-1,3,5-triazines that is 1,3,5-triazine-2,4-diamine in which the amino groups at positions 2 and 4 are respectively carrying 2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl and 2-(propan-2-ylsulfonyl)phenyl substituents. It is a potent inhibitor of anaplastic lymphoma kinase (ALK), Ack and ROS1 activity (IC50 values are 3.5, 5.8 and 8.9 nM respectively) and exhibits anti-cancer properties. It has a role as an antineoplastic agent, an apoptosis inducer, an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, an antimalarial and an EC 6.1.1.6 (lysine--tRNA ligase) inhibitor. It is a secondary amino compound, a monomethoxybenzene, a N-methylpiperazine, an aromatic amine, a diamino-1,3,5-triazine, a member of piperidines and a sulfone.

storage

Store at -20°C

References

[1] kuromitsu s, mori m, shimada i, et al. anti-tumor activity of asp3026, a novel and selective alk inhibitor of anaplastic lymphoma kinase (alk).annual meeting of the american association for cancer research (aacr), orlando, fl. 2011.
[2] mori m, ueno y, konagai s, et al. the selective anaplastic lymphoma receptor tyrosine kinase inhibitor asp3026 induces tumor regression and prolongs survival in non–small cell lung cancer model mice. molecular cancer therapeutics, 2014, 13(2): 329-340.
[3] george s k, vishwamitra d, manshouri r, et al. the alk inhibitor asp3026 eradicates npm-alk+ t-cell anaplastic large-cell lymphoma in vitro and in a systemic xenograft lymphoma model. oncotarget, 2014, 5(14): 5750-5763.