CaMKK2 Inhibitor Series

The line of up of different inhibitor series (hinge binders) for CaMKK2 that we are currently pursuing include: furopyridine, azaindole (pyrrolopyridine), quinoline, triazolopyridazine, imidazopyrazine, pyrazolopyrimidine. Figure 1. Figure 1: CaMKK2 hinge binders As part of our structure and activity relationships (SAR), we continue to build diversity on the pyridine ring for the furopyridine series, and Read More …

Current Progress on the Synthesis of CaMKK2 Inhibitors: Furopyridine Analogs

Following the successful synthesis of the furopyridine scaffold via an alternative synthetic route, conditions have been worked out to optimize yields on the synthesis of the key intermediate: 5-bromobenzofuran-3(2H)-one. Thus far the following set of analogs, Figure 1, have been generated by building diversity on the pyridine ring. These analogs together with with proposed others Read More …

CaMKK2 Inhibitors: Building Diversity Around the Core Furopyridine Scaffold

Preparation of CaMKK2 analogs Pursuant to our aim of preparing a library of small molecule chemical probes around our most promising core scaffold, furopyridine, we sought to develop different chemistries that would allow us to achieve this objective. In the original synthetic route, 5-bromofuro[2,3-b]pyridine, 1, was able to undergo the Suzuki cross-coupling reaction to install Read More …

Synthesis of BRSK2 Compounds

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 …

Project Overview: Preparation of Active Chemical Probes for CAMKK2 and BRSK2

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 …