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 biochemical processes including cellular growth, cell survival, cell motility and immune cell activation. Indeed kinases have emerged as of one the most successful drug target of the current century – leading to greater than 30 small molecule kinase inhibitors approved by the US FDA.
I have the privilege of working on two (2) interesting projects – generating a library of chemical probes for the ongoing CAMKK2 project and more recently BRSK2 – both of which are understudied protein kinases. Our goal is to develop potent, selective and cell active compounds as CAMKK2 and BRSK2 chemical probes.
Our aim is to prepare large numbers of small molecule chemical probes via robust synthetic chemistry that will enable fast and efficient diversification (SAR) around our core scaffolds – Furopyridines, pyrrolopyridines, quinolines and other hinge binders.
A series of small molecule aminoquinolines have recently been published in the Journal of Medicinal Chemistry that inhibit mutant B-Raf kinase activity both in vitro and in vivo. These aminoquinolines are also found to be active in inhibiting BRSK2 kinase activity. To this end, we are preparing a series of aminoquinolines to confirm the reported BRSK2 inhibitory activity and ultimately design small molecules that would be selective for BRSK2. Early indications on the initial analog of this series suggests the aminoquinolines offers a great starting to this drug discovery effort.
I will be providing details of my synthetic strategies and data as I receive them in the course of time.
Many thanks to entire the SGC-UNC team, particularly to David, Alison, Tim and Kim.