A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
Introduction Situation Kinases are useful for drug discovery – many opportunities! Kinase by kinase probe development is important, but it will take too long to discover a probe for each kinase Disease relevant phenotypic assays need smart compounds sets Numerous high quality kinase inhibitors exist in the literature and in company collections Kinases are “connected” Read More …
It’s never too late to take another look at your data. The incredibly knowledgeable Sally Cowley suggested that I shouldn’t just think about how many cells contain any AlexFluor488 antibody after electroporation, but how bright each cell is (i.e. the amplitude of fluorescence). Looking at this instead will give me an idea of how much Read More …
Written in collaboration with Tigran M. Abramyan (Alexander Tropha’s lab at UNC Chapel Hill) In my previous open lab notebook entry I described the in silico approach using the program SparkTM to grow fragments found to co-crystallize within binding site A of the transcription factor brachyury to compounds with hopefully higher binding potency. The overall aim Read More …
Protein STK17A or DRAK1 is a serine/threonine kinase that belongs to the death-associated protein kinase family (DAPK). This family is comprised of five members: DAPK1, DAPK2, DAPK3, DRAK1 and DRAK2, being the last two the least studied. As part of our efforts to find inhibitors for understudied kinases, we recently disclosed a high quality chemical Read More …
As part of SGC-UNC’s scaffold hopping strategy to identify new series of compounds active against CaMKK2, we recently submitted a select number of compounds differing in hinge-binder for CaMKK2 enzyme inhibition assay. The hinge-binders included thienopyridine, furopyridine, quinoline, thienopyrimidines, pyrimidine, N-methyl azaindoles and quinazoline, Figure 1. Others are azaindoles, triazolopyridazine, pyrazolopyridine, imidazopyridine etc. Figure 1: Read More …
The protein kinase N3 (PKN3) represents one of the understudied kinases in the human kinome and therefore one of the kinases SGC-UNC wants to target. As part of the UNC-SOLAR program, a summer program for students, Guillermo Correa Otero was working with me in the lab for 9 weeks. Under the supervision of David Drewry, Read More …
Scaffold hopping is a strategy utilized in medicinal chemistry where the core chemical structure of a promising drug candidate is replaced isosterically, which leads to structurally novel compounds. There are many reasons for undertaking this exercise including; improving potency, changing physiochemical properties such as solubility and clogP, enhance ADME properties and to move into new Read More …
Dear colleagues, I want to share with you all the poster presented this past spring 2019 at The American Chemical Society (ACS) National Meeting in Orlando, FL. This summaries our work on the synthesis of DRAK2 inhibitors.
As soon as possible I’m hoping to use CRISPR/Cas9 genetic editing to make sets of DIPG patient cells that differ only in one gene (either with/without the whole gene or with/without mutations of interest). This will allow me to make far more accurate comparisons of behaviour between the cells in relation to specific genes or Read More …
Access to large amounts of core building blocks is essential in drug discovery programs. It enables rapid synthesis of a series which can then give structure activity relationships (SAR) of the drugs and their target. SAR data allows medicinal chemists to determine the group(s) in a structure evoke a change in activity, whether positive or Read More …
