WH-4-023

This is a very promiscuous tyrosine kinase inhibitor.

WH-4-023 is compound 28 in the referenced work. However, this compound is one of a number synthesised, and the actual paper discusses detailed profiling of a compound 43. This later compound is more potent in cells, is better characterised in terms of its kinase selectivity, and has in vivo data presented (PK and PD). It is not clear how compound 28 has received the designation of WH-4-023 in preference to the true subject of the paper (Compound 43). In the absence of any detailed profiling of 28 it cannot be recommended as a suitable probe. This is also not a recommendation of compound 43 - that should be considered separately. Both compounds, and the series in general would appear to be potent pan SRC/LCK-family inhibitors, and possess a number of other activities, including a range of sub uM kinase activities not always associated with SRC-family inhibition. Much more selective probes for LCK exist, see for example A-770041 from Abbott.

This appears to be non-selective versus Src. Further kinase profiling is needed prior to recommendation as a probe for Lck.

Poor bioavailability hampers use of WH-4-023 as in vivo probe in mice.