Donated Chemical Probes

Target	DDR1 DDR2 MAPK11 MAPK14
Targeted domain	Kinase domain (active site)
Mode of action	Inhibitor (type 2, ATP competitive)
Control	SR-301
Recommended cellular usage concentration	100 nM
In vivo use	No
Donated by	SGC-Frankfurt

Inhibitor/agonist potency: goal is < 100 nM (IC₅₀, K_d)	Surpasses criterion: Enzyme kinetic assay from"Reaction Biology": DDR1: IC₅₀ = 53.3 nM (ATP conc.: 100 µM), DDR2: IC₅₀ = 0.75 nM (ATP conc.: 5 µM), MAPK11: IC₅₀ = 45.1 nM (ATP conc.: 50 µM), MAPK14: IC₅₀ =6.2 nM (ATP conc.: 2.5 µM)
Selectivity within target family: > 30-fold	Closest off-targets found in KinomeScan: ABL1, RIPK2, RPS6KA5, CHEK2, STK38L; for all IC₅₀ > 25 µM (> 125 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: NanoBRET assay (HEK293T cells, full-length protein): DDR1: IC₅₀ = 23 ± 2 nM, DDR2: IC₅₀ = 18 ± 2 nM, MAPK11: IC₅₀ = 196 ± 8 nM, MAPK14: IC₅₀ =125 ± 11 nM Destabilizing effect on E-cadherin
Control compound (100 times less potent than the probe)	SR-301: NanoBRET assay (HEK293T cells, full-length protein): DDR1: IC₅₀ = 21.9 ± 5.44 µM (>850 fold), DDR2: IC₅₀ = 15.5 ± 5.08 µM (>850 fold), MAPK11: IC₅₀ = 1.83 µM (8- fold), MAPK14: IC₅₀ =5.39 ± 3.10 µM (43-fold)