HP163

**HP163** is a second-generation, non-toxic small molecule antagonist of the aryl hydrocarbon receptor (AHR) developed by Hercules Pharmaceuticals for oncology and antiviral applications. It inhibits AHR activation by kynurenine (Kyn), a metabolite produced during viral infections, thereby suppressing AHR-mediated interference with type I interferon (IFN-I) production, NF-κB signaling, and promyelocytic leukemia (PML) protein-driven intrinsic antiviral immunity. Preclinical studies demonstrate oral bioavailability (51%) with 25% blood-brain barrier penetration; in Zika virus (ZIKV)-infected pregnant mice, HP163 (2.5 mg/kg) reduced fetal viral loads in brain, eyes, spleen, and placenta, prevented microcephaly, ventricular dilation, cortical thinning, intrauterine growth restriction, and preserved neural progenitor cells while decreasing microglial activation.[1][2][3]