Table 1. The Inhibitory activity and selectivity of acridine analogs of DYRK2.
Table 1—source data 1. Raw data of inhibitors against kinases for Table 1.
elife-77696-table1-data1.zip (83.7KB, zip)
| Cmpd. |
|
IC50 at molecular level (nM) | Selectivity | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R1 | R2 | R3 | R4 | DYRK2 | DYRK1A | DYRK1B | DYRK3 | Haspin | MARK3 | DYRK2&DYRK1A | DYRK2&DYRK1B | DYRK2&DYRK3 | DYRK2&Haspin | DYRK2&MARK3 | |
| LDN192960 |
|
-CH3 | -CH3 | -H | 53 ± 2 | 1859 ± 30 | 2900 ± 39 | 22 ± 4 | 18 ± 2 | 611 ± 19 | 35 | 55 | ~ | ~ | 12 |
| 1 |
|
-CH3 | -CH3 | -H | 38 ± 2 | 651 ± 29 | 1401 ± 91 | 115 ± 4 | 34 ± 3 | 36 ± 2 | 17 | 17 | 3 | ~ | ~ |
| 2 |
|
-CH3 | -CH3 | -H | 31 ± 1 | 731 ± 36 | 1477 ± 128 | 94 ± 9 | 27 ± 3 | 27 ± 5 | 24 | 48 | 3 | ~ | ~ |
| 3 |
|
-CH3 | -CH3 | -H | 41 ± 2 | 1018 ± 78 | 2495 ± 88 | 157 ± 18 | 24 ± 1 | 33 ± 7 | 25 | 61 | 4 | ~ | ~ |
| 4 |
|
-CH3 | -CH3 | -H | 53 ± 2 | 964 ± 14 | 1386 ± 21 | 234 ± 10 | 30 ± 1 | 96 ± 3 | 18 | 26 | 4 | ~ | 2 |
| 5 |
|
-CH3 | -CH3 | -H | 89 ± 2 | 1026 ± 96 | 3488 ± 86 | 311 ± 22 | 53 ± 4 | 91 ± 5 | 12 | 39 | 3 | ~ | 1 |
| 6 |
|
-CH3 | -CH3 | -H | 20 ± 3 | 889 ± 131 | 697 ± 67 | 110 ± 11 | 45 ± 3 | 100 ± 4 | 44 | 35 | 6 | 2 | 5 |
| 7 |
|
-CH3 | -CH3 | -CH2OH | 13 ± 1 | 2844 ± 49 | 2049 ± 116 | 26 ± 2 | 65 ± 5 | 107 ± 4 | 219 | 158 | 2 | 5 | 8 |
| 8 |
|
-CH3 | -CH3 | -COOH | 342 ± 77 | 7713 ± 1,249 | 6311 ± 1,380 | 8009 ± 130 | 308 ± 26 | 1613 ± 24 | 23 | 18 | 23 | ~ | 5 |
| 9 |
|
-CH3 | -CH3 | -CH2NH2 | 797 ± 26 | 8774 ± 508 | 7799 ± 81 | 665 ± 28 | 716 ± 48 | 3390 ± 301 | 11 | 10 | ~ | ~ | 4 |
| 10 |
|
-CH3 | -CH3 | -CF2H | 522 ± 210 | 53206 ± 16,384 | 47964 ± 3,582 | 402 ± 13 | 163 ± 21 | 460 ± 25 | 102 | 92 | ~ | ~ | ~ |
| 11 |
|
-Bn | -CH3 | -H | 646 ± 164 | 139908 ± 677 | 4975 ± 328 | 2026 ± 600 | 1608 ± 52 | 555 ± 36 | 217 | 8 | 3 | 3 | ~ |
| 12 |
|
-Bn | -CH3 | -H | 427 ± 109 | 12504 ± 3,260 | 8203 ± 674 | 539 ± 353 | 1085 ± 139 | 1062 ± 54 | 29 | 19 | 1 | 3 | 2 |
| 13 |
|
-Bn | -CH3 | -H | 124 ± 27 | 21608 ± 3,431 | 2812 ± 543 | 1142 ± 129 | 1588 ± 40 | 359 ± 17 | 174 | 23 | 9 | 13 | 3 |
| 14 |
|
-iPr | -CH3 | -H | 85 ± 17 | 984 ± 127 | 3787 ± 234 | 93 ± 28 | 300 ± 21 | 215 ± 12 | 12 | 45 | 1 | 4 | 3 |
| 15 |
|
-Bn | -Bn | -H | 623 ± 18 | 19244 ± 1,551 | 21110 ± 1,388 | 496 ± 36 | 18643 ± 1,365 | 1183 ± 127 | 31 | 34 | ~ | 30 | 2 |
| 16 |
|
-CH3 | -CH3 | -CH2OH | 25 ± 9 | 2243 ± 74 | 2257 ± 279 | 33 ± 6 | 90 ± 9 | 134 ± 8 | 90 | 90 | 1 | 4 | 5 |
| 17 |
|
-CH3 | -CH3 | -CH2OH | 9 ± 2 | 2145 + 100 | 2272 + 134 | 68 + 5 | 26 + 5 | 87 + 7 | 240 | 252 | 8 | 3 | 10 |
| 18 |
|
-CH3 | -CH3 | -CH2OH | 18 ± 2 | 1250 ± 95 | 1222 ± 168 | 73 ± 13 | 16 ± 3 | 116 ± 13 | 69 | 68 | 4 | ~ | 6 |
| 19 |
|
-CH3 | -CH3 | -CH2OH | 23 ± 3 | 1531 ± 52 | 3443 ± 294 | 108 ± 17 | 50 ± 1 | 210 ± 4 | 67 | 150 | 5 | 2 | 9 |
| 20 |
|
-CH3 | -CH3 | -CH2NC(NH2)2 | 1498 ± 104 | 21535 ± 1910 | 25850 ± 1,571 | 8477 ± 655 | 26509 ± 733 | 25535 ± 1,385 | 14 | 16 | 6 | 18 | 17 |
| 21 |
|
159 ± 7 | 3014 ± 137 | 3514 ± 511 | 69 ± 6 | 1564 ± 252 | 1315 ± 87 | 19 | 22 | ~ | 10 | 8 | |||
| 22 |
|
3761 ± 202 | 24733 ± 1,669 | 25948 ± 540 | 2426 ± 257 | 9750 ± 127 | 16770 ± 1,788 | 7 | 7 | ～ | 3 | 4 | |||