SR-318
| Target | MAPK14 |
| Targeted domain | Kinase domain (active site) |
| Mode of action | Inhibitor (type 2, ATP competitive) |
| Control | SR-321 |
| Orthogonal probe | Skepinone-L FS-694 |
| Recommended cellular usage concentration | < 100 nM |
| In vivo use | No |
| Donated by | SGC Frankfurt |
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd>/sub>) | Surpasses criterion: MAPK14: IC50 =5 nM; MAPK11: IC50 =32 nM (Radiometric activity assay ProQinase) |
| Selectivity within target family: > 30-fold | Surpasses criterion: Closest off-targets found in KinomeScan: DDR1, DDR2, KIT, MAP3K20, RPS6KA6, MYLK4 are > 200 fold selective in NanoBRET assay |
| Selectivity outside target family | Clean PDSP scan (45 targets) |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | Surpasses criterion:NanaoBRET: MAPK14 IC50 =3.7 nM; MAPK11 IC50 = 10 nM (full-length protein in HEK cells); Western: inhibition of HSP27 (Ser82) < 1μM |
| On target cell activity for secreted targets: appropriate alternative such as mouse model or other mechanistic biological assay, e.g., explant culture | Inhibition of TNFα release in WB: IC50 = 283 nM |
| Control compound (100 times less potent than the probe) | Surpasses criterion: SR-321: IC50 MAPK14 = 13 µM and MAPK11 = 11 µM (NanoBRET), DDR2: IC50 = 220 nM (NanoBRET), but no other kinase activity.Clean PDSP scan except for one off-target: TMEM97 Ki =2887.53 nM |