Table 2.
Compound | Scaffold | n | R | TTBK1 intact cell NB IC50 (µM)[a] | TTBK1 permeabilized cell NB IC50 (µM)[b] | TTBK2 intact cell NB IC50 (µM)[a] | TTBK2 permeabilized cell NB IC50 (µM)[b] | Kinetic solubility (µM) |
---|---|---|---|---|---|---|---|---|
1 | A | 1 | > 30 | 2.5 | 16 | 3.6 | NT[c] | |
AMG28 | A | 2 | 20.9 ± 1.4[e] | 2.88 ± 0.26[e] | 12.6 ± 0.9[e] | 4.10 ± 0.65[e] | NT | |
2 | A | 3 | > 30 | 19 | > 30 | 17 | NT | |
3 | B | N/A[d] | 15.8 ± 3.3[e] | 2.34 ± 0.31[e] | 11.7 ± 3.7[e] | 2.52 ± 0.62[e] | 133 | |
4 | A | 2 | > 30 | 20 | > 30 | > 30 | NT | |
5 | A | 2 | > 30 | 7.2 | 26 | 9.3 | NT | |
6 | A | 2 | > 30 | 25 | > 30 | 19 | NT | |
7 | A | 2 | > 30 | > 30 | > 30 | > 30 | NT | |
8 | A | 2 | > 30 | > 30 | > 30 | > 30 | NT | |
9 | A | 2 | 12.7 ± 0.7[e] | 2.11 ± 0.43[e] | 6.40 ± 1.17[e] | 1.47 ± 0.36[e] | 50 | |
10 | A | 2 | 11.1 ± 2.0[e] | 1.97 ± 0.00[e] | 6.39 ± 1.59[e] | 1.39 ± 0.44[e] | 131 | |
11 | A | 2 | > 30 | > 30 | > 30 | > 30 | NT |
aAssay executed in intact HEK293 cells. bAssay executed in permeabilized HEK293 cells. cNT: not tested. dN/A: not applicable. eData representative of two biological replicates ± SEM.