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Probe
ALW-II-49-7 is in
the process of SERP review.
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Information
DDR2
DDR1
Type II
up to 5 uM
Reviewer recommended concentration:
1 - 2 µM compound is effective and avoids off-target effects
Potency assay (off target):
Profiled at a concentration of 1 μM against a diverse panel of 353 kinases by DiscoverX.
Identified Off-targets: RAF1 (IC50 of 22 nM), LYN (IC50 of 257 nM)
A useful inhibitor although has RAF1 as an off-target (IC50 = 22 nM). May have more off-targets based on the published kinome profiling data.
(last updated:
17 May 2023 )
SERP+
Ratings
In Cell Rating
SERP+
Comments:
Compound ALW-II-49-7 (in the original publication as "compound 1") shows potent in vitro inhibition of DDR1, DDR2, RAF1 and LYN showing IC50s of 12.4 nM, 18.6 nM, 22 nM and 257 nM respectively. The selectivity has been evaluated thoroughly using KinomeScan against 353 kinases at 1 µM concentration. The in cellulo potency was evaluated using Western blotting monitoring autophosphorylation of DDR2 (HEK 293T cells), which gave only rough estimation of in cellulo potency (EC50 of approx. 500 nM). Considering the cytotoxicity profile, selectivity profile and in cellulo potency, I recommend 2 µM concentrations as the highest suitable concentration for cellular experiments. As of June 2024, there are no DDR1/2 tool compounds that would be exclusively selective for DDR1/2 only. Therefore, ALW-II-49-7 represents one of the best compounds that are currently available for studying DDR1/2 biology, despite its drawbacks. In addition, the original publication disclosed also analogue "compound 3" that exhibits slightly better selectivity profile across the kinome but lacks further profiling. Of note, negative control compound is missing. Therefore, it is highly advisable to use ALW-II-49-7 together with orthogonal tool compounds such as BAY-826 and BAY-309 (probe and neg. control).
