Table 3.

SAR of 6-aryl substituents

				KinaseSeeker a			NanoBRET b
Entry	Compound	Scaffold	Ar	STK17A (% I)	STK17B (% I)	STK17B IC50 (nM)	STK17B IC50 (nM)
1	11b	C		12	94	49 ± 12	500 ± 20
2	11c	C		30	90	110 ± 12	1700 ± 400
3	11d	C		0	90	49 ± 7.9	>10,000
4	11e	C		0	90	41 ± 6.9	380 ± 62
5	11f	C		8	96	28 ± 3.4	120 ± 6
6	11g	C		0	88	59 ± 8.0	550 ± 100
7	11h	C		0	83	62 ± 9.0	530 ± 46
8	11i	C		0	91	92 ± 6.7	310 ± 30
9	11j	C		0	81	110 ± 12	>10,000
10	19c	D		23	43	—	>10,000 c
11	19d	D		0	18	—	>10,000 c
12	19e	D		6	46	880 ± 120	>10,000 c
13	19f	D		0	3	—	>10,000 c

^aKinaseSeeker split luciferase binding assay. % I, inhibition compared to control (DMSO) at 1 μM, n = 2, data ± 10%. IC₅₀, determined by dose response, n = 2 ± SD. — not determined.

^bTarget engagement determined by NanoBRET assay in HEK293 cells, n = 3 ± SE.

^cn = 1.