Understudied Kinases

Synthetic highlights for CLK inhibitors and ‘Shiny Science’

Posted onAuthorCarla Alamillo-Ferrer4 Comments

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 …

Synthesis of a selective inhibitor for DRAK2 kinase

Posted onAuthorAlfredo PicadoLeave a comment

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 …

Introduction to my KCGS CDK family project

Posted onAuthorCarla Alamillo-Ferrer1 Comment

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 …

Optimising transfection of the C2C12 myoblast cell line

Posted onAuthorElizabeth Brown2 Comments

Within a month (hopefully) I’ll be convincing C2C12 myoblast cells to express all kinds of mutant ALK2 to test its activity and interactions with other proteins within the cell. I’ll be doing this by treating them so that they’ll take up pieces of circular DNA (plasmids) that express those mutant proteins (i.e. transfecting them). Seeing Read More …

Structure Activity Relationship (SAR) study to identify Nek4 inhibitors:

Posted onAuthorNirav KapadiaLeave a comment

Hello! Recently, I co-authored a manuscript titled, “In depth analysis of kinase cross screening data to identify chemical starting points for inhibition of the Nek family of kinases” [http://pubs.rsc.org/en/content/articlelanding/2018/md/c7md00510e#!divAbstract]. As a part of this manuscript we identified several chemical starting points that can be used for the design of narrow spectrum and potent Nek kinase Read More …

Chemical probes for understudied kinases

Posted onAuthorAlfredo PicadoLeave a comment

One of the ongoing projects at SGC-UNC is the development of chemical probes for understudied kinases (e.g. MST1-4, TAOK1-3, DCAMKL1, MAP3K2 and MAP3K3). A chemical probe is defined as a small molecule that selectively and potently modulates a protein’s function. Generating chemical probes for understudied kinases is important so we can further understand the biology Read More …

Project Overview: Work towards a CLK probe

Posted onAuthorCarla Alamillo-Ferrer1 Comment

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 …