GNF179

GNF179 is an optimized imidazolopiperazine (IZP) antimalarial compound developed by the Genomics Institute of the Novartis Research Foundation (GNF), the Scripps Research Institute, and Novartis. It is a close chemical analogue of ganaplacide (KAF156), differing by a single halogen. GNF179 exhibits potent, broad-spectrum activity against multiple stages of the Plasmodium life cycle, including asexual blood stages, liver stages, and transmissible gametocytes, and is active against both drug-sensitive and drug-resistant strains (including artemisinin-resistant strains). Its mechanism of action involves targeting the Plasmodium intracellular secretory pathway, specifically binding to and inhibiting the essential dynamin-like GTPase SEY1 (Synthetic Enhancement of YOP1), which disrupts endoplasmic reticulum (ER) membrane fusion, ER architecture, and protein trafficking.