Chiesi Farmaceutici's recent disclosure of CHF-6523, an inhaled PI3Kδ inhibitor, raises questions about the suitability of PI3Kδ as a therapeutic target for Chronic Obstructive Pulmonary Disease (COPD). The development suggests that despite initial promise, targeting PI3Kδ may present challenges in effectively managing COPD.
Emerging NLRP3 Inflammasome Inhibitors
Concurrently, there's a notable increase in the development of (pre)clinical compounds that inhibit the NLRP3 inflammasome. Many of these compounds feature a hexahydroindacene ring system. Nodthera’s ND-0796 is one such example, highlighting the growing interest in this class of inhibitors.
AstraZeneca and Mitsubishi Tanabe's AZD4144
AstraZeneca (AZ) and Mitsubishi Tanabe have jointly disclosed their clinical compound, AZD4144, which is currently undergoing Phase I trials in healthy volunteers. The discovery process involved overcoming significant hurdles, including phospholipidosis (PLD), genotoxicity, and hERG inhibition. These challenges were addressed within a non-classical pharmacophore series. Anders Johansson presented the details of this discovery at the EFMC-ISMC 2024 Meeting in Rome, emphasizing the complexities of developing safe and effective drugs.
