We're delighted to announce that Dr. Valerio Falasca has published a new paper titled "Design and Synthesis of Novel Isoflavene TANK-Binding Kinase 1 Inhibitors With Anti-Inflammatory Activity" in ChemMedChem.
In this study, the team designed, synthesised and biologically evaluated anti-inflammatory TBK1 inhibitors based on isoflavonoid natural product scaffolds. Chronic inflammation accounts for more than half of all global deaths and is associated with many diseases including cancer, heart disease, and diabetes. TBK1 is a key mediator of several inflammatory pathways, and its inhibition shows great promise for overcoming autoimmune diseases, hyper-inflammatory diseases, neurodegenerative diseases, and cancer resistance.
A novel series of TBK1 inhibitors was synthesised via the multicomponent Petasis reaction, guided by molecular modelling and SAR studies on isoflavonoid derivatives with established anti-inflammatory activity. The results support an alternative approach to disrupting TBK1 inflammatory signalling compared to conventional kinase inhibition, which can produce off-target effects on other kinases. The lead compound, 7a, showed potent inhibitory activity against NF-κB and type I IFN inflammatory signalling pathways (IC50 = 0.13 µM), representing a 6.7-fold improvement in potency over the parent isoflavene scaffold.
Publication details:
- Journal: ChemMedChem
- Title: Design and Synthesis of Novel Isoflavene TANK-Binding Kinase 1 Inhibitors With Anti-Inflammatory Activity
- Authors: Valerio Falasca, W. Samantha N. Jayasekara, Dominic De Nardo, Daniel S. Wenholz, Michael P. Gantier, and Naresh Kumar
- Published: 12 July 2026
- DOI: 10.1002/cmdc.70376
Congratulations to Dr. Valerio and all co-authors on this outstanding achievement! We are proud of your contributions to advancing medicinal chemistry research.
A particularly fitting moment came at the recent RSC conference in Perth, where Dr. Valerio Falasca reconnected with Professor Naresh Kumar — former PhD student and supervisor reunited, celebrating new science and connection built through years of research.