Are kinase DRAK2 inhibitors active against kinase AURKB in cells? Good news: NO!

The original compound donated by Pfizer PFE-PKIS 43 (thienopyrimidine scaffold), showed activity against 3 kinases greater than 70% inhibition in the KinomeSCAN at 1 µM (STK17B/DRAK2, AURKB and SRPK2).

In the series of compounds recently synthesized as thienopyrimidine derivatives we seek selective and potent inhibitors for STK17B/DRAK2 only.

To further identify off-target activity of these compounds, NanoBRET assays were implemented in our laboratory to test their potency (IC50) with AURKB and STK17A/DRAK1 in cells.  These cellular assays were performed by Carrow Wells and Julie Pickett.

A set of STK17B/DRAK2 inhibitors were tested against AURKB, results are shown below.

Table 1. Potency of selected compounds against AURKB and DRAK2

Table 1 shows good news in terms of selectivity.  All thienopyrimidine compounds resulted inactive towards AURKB while maintaining good cellular potency with DRAK2.  AP-39 shown an IC50 = 19 µM for DRAK1 in the nanoBRET. Compound KW-2449 was used as a control.

Figure 1. Activity of compound AP-39 with kinase AURKB, nanoBRET assay.


Leave a Reply

Your email address will not be published. Required fields are marked *