A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
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 …
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 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 …
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 …
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 …
Preparation of GW807982X analogues can be find in Tavares’s patent from 2004 (WO2004/35588, 2004, A1). This involves a 4‑step synthesis starting from commercially available 3,6-dichloropyridazine (see previous blog, https://openlabnotebooks.org/project-overview-work-towards-a-clk-probe). From my experience in the lab, formation of the highly nitrogenated pyrazolopyridazine 3 is not a trivial step. This is probably because the formation of the charged Read More …
Towards the SGC goal of creating a kinase chemogenomic set (KCGS) we have been receiving and profiling kinase inhibitors donated by pharmaceutical companies. One such compound is PFE-PKIS 43 (Scheme 1a). We received this compound from Pfizer and it was screened against 403 kinases at DiscoverX. This compound, originally synthesized and published as part of Read More …
