Table 3. JNK inhibitors potency on potential off-targets.
Enzymatic IC50 or dissociation constant (Kd) for the potential additional kinase targets. For JNK-IN-7 and JNK-IN-11, the kinases with the score below 5 were tested and for JNK-IN-8 and JNK-IN-12 kinases with score below 1 were tested (see profiling in table S4). See also Tables S1 and S3.
| JNK-IN-7 | JNK-IN-8 | JNK-IN-11 | JNK-IN-12 | ||||
|---|---|---|---|---|---|---|---|
| kinase | IC50 (nM) | kinase | IC50 (nM) | kinase | IC50 (nM) | kinase | IC50 (nM) |
| (enzymatic) | (enzymatic) | (enzymatic) | (enzymatic) | ||||
| JNK1 | 1.5 | JNK1 | 4.7 | JNK1 | 1.3 | JNK1 | 13 |
| JNK2 | 2 | JNK2 | 18.7 | JNK2 | 0.5 | JNK2 | 11.3 |
| JNK3 | 0.7 | JNK3 | 1 | JNK3 | 0.5 | JNK3 | 11 |
| IRAK1 | 14.1 | MNK2 | 238 | EGFR(L861Q) | 21 | IRAK1 | 37.6 |
| KIT | 2410 | FMS | 287 | EGFR(L858R) | 24.9 | HIPK4 | 57.1 |
| HIPK1 | 5010 | HIPK4 | 8970 | DDR1 | 56.1 | AKT2 | 89.9 |
| Kinase | Kd (nM) | KIT | >10000 | CSNK1E | 82.9 | AKT1 | >370 |
| (KinomeScan™) | MET(M250T) | >10000 | CSNK1G2 | 161 | AKT3 | >370 | |
| YSK4 | 4.8 | PDGFRB | >10000 | PDGFRB | 1030 | SLK | 884 |
| ERK3 | 22 | PRKX | 7500 | KIT | 1320 | ||
| RIOK2 | 30 | Kinase | Kd (nM) | Kinase | Kd (nM) | Kinase | Kd (nM) |
| (KinomeScan™) | (KinomeScan™) | (KinomeScan ™) | |||||
| PIP5K2C | 32 | KIT(V559D) | 92 | EGFR(G719C) | 2.6 | KIT(V559D,T670I) | 160 |
| CDKL5 | 34 | KIT(V559D,T670I) | 56 | EGFR(E746- A750del) |
7 | ||
| KIT(L576P) | 40 | MYLK4 | 4000 | KIT((V559D) | 8.2 | ||
| KIT(V559D) | 48 | RIOK2 | 120 | PFCDPK1 | 14 | ||
| ICK | 54 | DMPK2 | 18 | ||||
| DRAK1 | 100 | CIT | 95 | ||||
| DYRK2 | 120 | ERBB2 | 230 | ||||
| BIKE | 190 | PRKD3 | 240 | ||||