Table 1.

IC₅₀ and GR₅₀ determinations on different PDGFRA- and KIT-mutants and GIST cell lines of ligands 1-13

Cpd	HTRF IC50 [nM]		KIT CTG GR50 [nM]		PDGFRA CTG GR50 [nM]
	PDGFRA-D842V	KIT-D816H	GIST-T1a	T1-D816E	T1-a-D842V	T1-a- G680R	GIST-48Bb	ratio GIST-48B/ T1-a-D842V
ava (1)	<0.1	0.5 ± 0.1	36 ± 10	67 ± 18	15 ± 8	1563 ± 241	1340 ± 173	89
2	7324 ± 2078	9303 ± 1208	6731 ± 2073	9481 ± 1038	2733 ± 517	2000 ± 403	7967 ± 2792	3
3	5588 ± 2557	1541 ± 852	≥10,000	≥10,000	≥10,000	≥10,000	≥10,000	1
4	35 ± 13	76 ± 45	5271 ± 509	8739 ± 1321	1887 ± 545	≥10,000	≥10,000	5
5	0.6 ± 0.1	1.5 ± 1.0	1484 ± 1203	≥10,000	163 ± 47	≥10,000	≥10,000	61
6	7351 ± 884	2158 ± 167	≥10,000	≥10,000	≥10,000	≥10,000	≥10,000	1
7	749 ± 142	204 ± 84	709 ± 196	1962 ± 443	8216 ± 1475	≥10,000	≥10,000	1
8	0.4 ± 0.1	2.3 ± 1.7	254 ± 74	515 ± 94	58 ± 13	2600 ± 384	1933 ± 472	33
9	<0.1	0.4 ± 0.2	92 ± 16	235 ± 51	26 ± 5	2767 ± 459	4033 ± 653	155
10	<0.1	0.5 ± 0.1	39 ± 6	86 ± 19	26 ± 21	3311 ± 534	4833 ± 2564	186
11	<0.1	0.5 ± 0.2	39 ± 7	89 ± 23	24 ± 6	4033 ± 876	3467 ± 866	144
12	0.2 ± 0.1	0.6 ± 0.4	60 ± 12	131 ± 37	19 ± 6	3167 ± 58	4867 ± 1415	256
13	0.2 ± 0.1	2.0 ± 0.1	287 ± 176	637 ± 111	51 ± 7	5729 ± 435	≥10,000	196

Data presented as mean values ± s.d; n ≥ 3, where n represents the number of independent experiments.

T1-a cell lines: PDGFRA cell lines based on GIST-T1, generated by CRISPR/Cas9-mediated gene editing. Ava: avapritinib as reference inhibitor.

n.d. not determined, IC50 half-maximal inhibitory concentration, GR50 half-maximal growth inhibition rate.

^aGIST-T1 (RRID:CVCL_4976, Val560_Tyr578del).

^bControl cell line, which is neither KIT nor PDGFRA dependent and serves as an indicator for off-target toxicity.