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-ALK	TPX-0131	Crizotinib	Alectinib	Brigatinib	Ceritinib	Lorlatinib
Single EML4-ALK mutations
WT	0.4	50	7.4	12	3.9	0.8
I1171N	516	254	4,310	49	72	48
I1171S	189	188	306	31	27	31
I1171T	316	232	210	33	29	25
L1196M	0.5	274	50	21	5.4	38
L1198F	<0.2	18	397	74	618	30
G1202R	0.2	434	2,690	188	329	52
G1269A	13	451	197	20	15	49
G1269S	701	1,390	671	46	97	191
Compound EML4-ALK mutations
L1196M/L1198F	<0.2	252	2,250	253	1,410	1,310
L1198F/C1156Y	<0.2	19.3	776	102	1,310	140
L1198F/I1171N	1.6	626	236	55.1	64.1	78.7
G1202R/C1156Y	0.2	745	2,420	810	1,300	521
G1202R/L1196M	0.7	808	>10,000	1,100	1,260	4,780
G1202R/L1198F	<0.2	188	3,000	2,040	2,010	1,710
G1202R/G1269A	9.9	705	7,200	164	303	636
G1202R/G1269A/L1204V	14.9	634	6,740	176	345	673
G1202R/G1269A/L1198F	0.2	596	>10,000	907	1,670	6,330

Note: IC₅₀ values were determined from three independent replicates.