NVP-TAE684 is an aminopyrimidine-based, ATP-competitive inhibitor of ALK (IC50, 3 nM) with additional activity vs Flt3 and Tie2 at values of 3 nM, and 12 nM, respectively. Despite ALK's high sequence homology with insulin receptor kinase (InsR), cellular InsR potency of NVP-TAE684 in Ba/F3 Tel-Flt3 and Ba/F3 Tel-Tie2 cell lines was 554 nM and >1 uM, respectively. [1]

In human anaplastic large-cell lymphoma (ALCL) cell lines expressing NPM-ALK, NVP-TAE684 inhibits proliferation of Karpas-29 and SU-D HL-1 cell lines with an IC50 range of 2-5 nM. Additionally, NVP-TAE684 inhibits phosphorylation of downstream of both ERK and Akt in Karpas-299 cells, thus aiding in the confirmation that STAT, RAS/FAR/MAPK, and PI3K/Akt are activated by NPM-ALK in ALCL cell lines.

NVP-TAE684 has been shown to be efficacious in neuroblastoma lines with constitutively active ALK mutations (G1128A, I1171N, F1174L, R1192P, F1245C, R1275Q). [2] Additionally, NVP-TAE684 is effective in crizotinib-resistant EML4-ALK L1196M mutants as well as other secondary gatekeeper mutations. [2]

NVP-TAE684 is an aminopyrimidine-based, ATP-competitive inhibitor of ALK (IC50, 3 nM) with additional activity vs Flt3 and Tie2 at values of 3 nM, and 12 nM, respectively. Despite ALK's high sequence homology with insulin receptor kinase (InsR), cellular InsR potency of NVP-TAE684 in Ba/F3 Tel-Flt3 and Ba/F3 Tel-Tie2 cell lines was 554 nM and >1 uM, respectively. [1]

In human anaplastic large-cell lymphoma (ALCL) cell lines expressing NPM-ALK, NVP-TAE684 inhibits proliferation of Karpas-29 and SU-D HL-1 cell lines with an IC50 range of 2-5 nM. Additionally, NVP-TAE684 inhibits phosphorylation of downstream of both ERK and Akt in Karpas-299 cells, thus aiding in the confirmation that STAT, RAS/FAR/MAPK, and PI3K/Akt are activated by NPM-ALK in ALCL cell lines.

NVP-TAE684 has been shown to be efficacious in neuroblastoma lines with constitutively active ALK mutations (G1128A, I1171N, F1174L, R1192P, F1245C, R1275Q). [2] Additionally, NVP-TAE684 is effective in crizotinib-resistant EML4-ALK L1196M mutants as well as other secondary gatekeeper mutations. [2]