note: The Chemical Probes Portal only endorses
compounds as chemical probes for use as specific and
selective modulators of the proposed target if they
receive three or more (3-4) stars.
In vitro kinase assays at 300 nM CP43 using 70 different kinases. TAOK1 8%, TAOK2 11%, TAOK3 13% retained activity.
Three structurally related STE20 family members, LOK (48% activity retained), TAK1 (53% activity retained), and PAK2 (79% activity retained).
TAO1 Kinase Inhibitor is the only available probe for TOAK1/2. There are potential concerns about the selectivity of the probe over other kinases, as the in-vitro selectivity panel only consists of 70 kinases and TAOK3, LOK and TAK1 are also significantly inhibited . Therefore the cellular selectivity is unclear. There is no data available regarding other non-kinase off-targets and no orthogonal compounds or negative controls are available.
(last updated:
22 Mar 2023 )
SERP+
Ratings
In Cell Rating
SERP+
Comments:
The presented inhibitor displays high in vitro potency with 11 nM and 15 nM for TAOK1 and TAOK2, respectively. However, selectivity assessment is limited with only 70 kinases having been tested. Already, some off-targets have been identified to be inhibited by the compound. No non-kinase off-targets were studied. The assay was carried out at a concentration of only 0.3 uM. Antiproliferative effects were demonstrated for different cell-lines. No control compound is available. For cellular applications, a dose of >10 uM must be used, which is relatively large. The MoA was clarified by an ATP-competition assay. Since there are only very few selective TOAK inhibitors described, this compound can be provisionally considered as acceptable.
