A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
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 …
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 …
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 …
Another small set of compounds was recently synthesized, the major change in Set2 is the substitution of the sulfur atom by oxygen or nitrogen. The change was made in position 6 of the pyrimidine ring. These compounds along with others from Set1 are currently under screening in the NanoBRET cellular assay (performed by Carrow Wells).
After preparation of a set of GW807982X analogs, the next step was to get screening data against CLK1/2/3 at concentration of 1 uM at Luceome. For compounds that showed an inhibition of >75% on target they get a full dose response curve to generated IC50 values. To date, a set of 60 compounds have been synthesized Read More …
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 …
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 …
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 …
Over the past few weeks I’ve been perfecting a method for screening a small set of therapeutic compounds on DIPG cell lines. Before starting I made sure to discuss the techniques used in other groups to make sure that I design an assay that is comparable to theirs, although I may make my own changes Read More …
SNS-032 is a CDK2 inhibitor with an IC50 of 48 nM in cell-free assay and is 10 and 20-fold selective over CDK1 and CDK4 respectively (http://www.selleckchem.com/products/SNS-032.html). In my previous post (https://openlabnotebooks.org/introduction-to-my-kcgs-cdk-family-project/) I mention the aim to develop a narrow profile inhibitors for understudied kinase. To do so I have synthesized SNS-032 analogues since SNS-032 inhibits Read More …
