HH044

HH044 is a selective small molecule inhibitor of neuronal nitric oxide synthase (nNOS/NOS1). Developed through research involving Chapman University and Northwestern University, HH044 is designed to target the pro-tumorigenic effects of interferon-gamma (IFN-γ) in the melanoma tumor microenvironment. It functions by disrupting a positive feedback loop where nNOS-derived nitric oxide (NO) promotes the expression of COX-2 and the production of PGE2, which in turn further amplifies nNOS and PD-L1 expression. In preclinical melanoma models, HH044 has demonstrated the ability to reduce tumor PGE2 levels, inhibit tumor growth (particularly when used in combination with the COX-2 inhibitor celecoxib), and reactivate T cell responses by increasing IL-2 secretion in the presence of melanoma cells.