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 Read More …

CLK2 inhibitor candidates

In my previous post, I presented different CLK2 inhibitors (https://openlabnotebooks.org/clk-chemical-probe/), including structures, and IC50 curves that were generated using a cell target engagement assay called NanoBRET. My colleagues Carrow Wells and Julie Pickett generated these data. The BRET of NanoBRET stands for bioluminescence resonance energy transfer, and it is an in-vitro quantitative technique to identify Read More …

Synthesis of BRSK2 Compounds

BRSK2 Compounds NRF2 is a transcription factor that regulates the expression of antioxidant proteins and functions to protect against oxidative stress caused by inflammation. Under normal physiological conditions, NRF2 is degraded by KEAP1 and Cullin 3 (CUL3) through a process called ubiquitination (ubiquitin-dependent proteolysis). Following ubiquitination, it is transported to the proteasome where it is Read More …

Optimising an assay to detect alkaline phosphatase activity in C2C12 cells

I don’t just want to check whether the compounds I’m testing kill DIPG cells, I want to check that they’re doing this by altering BMP signalling too. However, I can’t do this with the DIPG cells, because if a compound does work, and kill them, there’ll be no cell left to actually measure the amount Read More …

Project Overview: Preparation of Active Chemical Probes for CAMKK2 and BRSK2

I provide herewith my first post –  A short overview of my current projects. Research at the SGC-UNC involves the preparation of active chemical probes for understudied protein kinases with the ultimate goal of designing potent small molecule inhibitors as treatment for diseases such as cancer. Kinases play critical roles in cellular signaling which controls important Read More …

Making single DIPG spheres

It’s usually a good idea to have more than one trick up your sleeve… So with that in mind, I’ve started developing another viability assay for my DIPG cell lines. The first assay relied on convincing a cell line that naturally grows as floating spheres to grow stuck down on the bottom of plastic wells, Read More …

Compound 11 update (SNS-032 analogues)

Following previous post, https://openlabnotebooks.org/sns-032-analogues-update/, compound 11 was chosen to further investigate the structure activity relationships (SAR) of the oxazole ring system with the hope to enhance potency and improve selectivity towards each respective target. The criteria to pick the building blocks to further study the SAR is based on electronics, size and shape. I have Read More …

First set of selected compounds against DRAK2 kinase

Several compounds derived from thienopyrimidine scaffolds were recently synthesized to be tested as inhibitors of DRAK2/STK17B kinase. Among these, a set of 12 were selected to determine their potency as IC50 values on a DRAK2 cellular assay. These compounds have different functional groups around the phenyl ring and variation in the position of the sulfur Read More …