Table 1. Hit rate for each member of the Nek family based upon screening data from large published screening sets with FLT3 values for comparison.
Compound set | PKIS a | PKIS2 b | BMS c | RBC d | Ambit e | GSK f | Millipore g |
No. of cmpds | 368 | 645 | 21 851 | 178 | 72 | 577 | 158 |
Nek1 | 0.011 | 0.051 | 0.001 | 0.051 | 0.014 | — | — |
Nek2 | 0.005 | 0.057 | 0.003 | 0.006 | 0.056 | 0.059 | 0.006 |
Nek3 | — | 0.031 | — | 0.006 | 0.014 | — | 0 |
Nek4 | — | 0.012 | — | 0.039 | 0.014 | — | — |
Nek5 | — | 0.065 | 0.0286 | — | 0.014 | — | — |
Nek6 | 0 | 0.023 | 0.017 | 0 | 0.042 | 0.031 | 0 |
Nek7 | 0 | 0.035 | 0.0315 | 0 | 0.042 | 0.035 | 0 |
Nek8 | — | — | — | — | — | — | — |
Nek9 | 0.033 | 0.051 | 0.009 | 0.028 | 0.042 | 0.016 | — |
Nek10 | — | 0.059 | — | — | — | — | — |
Nek11 | — | 0.031 | — | 0.011 | 0.042 | — | 0.095 |
FLT3 | 0.14 | 0.23 | 0.15 | 0.41 | 0.036 | 0.14 | 0.3 |
aValues for PKIS calculated by the number of compounds that inhibited each Nek by ≥50% divided by the total number of compounds screened (Elkins et al., 2016).
bValues for PKIS2 calculated by the number of compounds that inhibited each Nek ≥50% divided by the total number of compounds screened (Drewry et al., 2017).
cValues from Bristol-Myers Squibb screening data (hit rate calculated based on <13% of control) (Posy et al., 2011).
dValues from Reaction Biology Corporation data (Anastassiasdis et al., 2011).
eValues calculated from reported ambit Kd values – number of compounds that inhibit each Nek ≥500 nM divided by the total number of compounds (Davis et al., 2011).
fValues from GlaxoSmithKline screening taken from Nc ≤ 1 (Bamborough et al., 2008).
gValues calculated using EMD millipore screening data. Number of compounds that inhibit each Nek ≥50% divided by total number of compounds screened (Gao et al., 2013).