Carla Alamillo

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 …

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 …

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 …

At the SGC-UNC we are interested in building a set of inhibitors that “covers” the whole kinome. Here’s a reference that talks about our plans for the Kinase Chemogenomic Set (KCGS): http://journals.plos.org/plosone/article/related?id=10.1371/journal.pone.0181585. We are building the set with what we call “narrow spectrum” inhibitors – inhibitors that inhibit only a small set of kinases. To help Read More …

Hello everyone! This is my first post on the blog and I am going to give a brief summary of my main project as a Postdoctoral Research Associate at SGC-UNC. Protein phosphorylation is a quick and reversible mechanism with the aim to control biological functions. This mechanism involves structural conformational changes by adding a phosphate Read More …