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. Author manuscript; available in PMC: 2021 Dec 10.
Published in final edited form as: J Med Chem. 2020 Nov 20;63(23):14626–14646. doi: 10.1021/acs.jmedchem.0c01174

Table 2.

Initial SAR

graphic file with name nihms-1655834-t0011.jpg
KinaseSeeker a NanoBRET b
Entry Compound Scaffol
d		 X R1 R2 STK17
A (% I)		 STK17
B(% I)		 STK17B
IC50 (nM)		 STK17B
IC50 (nM)
1 4 A S OH SCH3 15 90 20 ± 3.9 210 ± 40
2 11a A S OH Cl 3 90 39 ± 8.2 680 ± 190
3 12 A S NH2 SCH3 1 61 — >10,000c
4 14 A O OEt Cl 4 36 — >10,000 c
5 15 A O OH Cl 0 36 — >10,000 c
6 16a A NH OEt SCH3 4 0 — >10,000 c
7 16b A NH OH SCH3 d d — >10,000 c
8 19a B S OH SCH3 0 26 — >10,000 c
9 19b B S OH OCH3 14 18 — >10,000
a

KinaseSeeker 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.

b

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

c

n = 1.

d

not determined due to assay interference.