Table 2.

Inhibitory activity (IC50) of TPX-0131 and other ALK inhibitors in Ba/F3 cell proliferation assays against single and compound EML4-ALK mutations.

Cell proliferation IC50 value (nmol/L)
EML4-ALKTPX-0131CrizotinibAlectinibBrigatinibCeritinibLorlatinib
Single EML4-ALK mutations
WT0.4507.4123.90.8
I1171N5162544,310497248
I1171S189188306312731
I1171T316232210332925
L1196M0.527450215.438
L1198F<0.2183977461830
G1202R0.24342,69018832952
G1269A13451197201549
G1269S7011,3906714697191
Compound EML4-ALK mutations
L1196M/L1198F<0.22522,2502531,4101,310
L1198F/C1156Y<0.219.37761021,310140
L1198F/I1171N1.662623655.164.178.7
G1202R/C1156Y0.27452,4208101,300521
G1202R/L1196M0.7808>10,0001,1001,2604,780
G1202R/L1198F<0.21883,0002,0402,0101,710
G1202R/G1269A9.97057,200164303636
G1202R/G1269A/L1204V14.96346,740176345673
G1202R/G1269A/L1198F0.2596>10,0009071,6706,330
  • Note: IC50 values were determined from three independent replicates.