CCT251236

This is a useful probe for Pirin - useful to study Pirin function both in cells and in vivo. There is a correlation of molecule binding to Pirin and cellular activity. Active and inactive versions of the molecule have been reported, and the inactive version should be used as a control.

CCT251236 has been thoroughly investigated and characterized as a cellular probe for Pirin (target) and HSF (pathway) and is supported by a robust and transparent set of data. My only concern is for possible in vivo use where there is an apparent non-linear pharcacokinetic response in mouse (20 mg/kg, oral dose gave a 3-fold lower AUC than a 5 mg/kg dose, albeit in a different mouse strain). I suggest users run a pilot PK study in their strain of interest to ensure the required exposures can be achieved with their dose.

While CCT251236 clearly shows potent binding (SPR) to human pirin, displays potent inhibition of Hsp72 induction in a cell-based assay (ELISA), and shows activity in an SK-OV-3 mouse xenograft study, this chemical probe may well be active against other targets, since the anti-proliferative activity against a panel of cancer cell lines is often more potent than the potency measured by the assays outlined above.  The enduser should thus use caution when interpreting cell-based or in vivo results obtained using CCT251236.