Nivelon

Nivelon is a small-molecule inhibitor that was first reported by a research team at the Institute for Molecular Medicine in 2014. The compound is structurally related to the class of indole‑based kinase inhibitors and was identified through a high‑throughput screen aimed at discovering novel modulators of the p38 MAPK signaling pathway. Chemical synthesis of nivelon involves a palladium‑catalysed cross‑coupling reaction between a 5‑methoxyindole derivative and a bromobenzyl ketone, followed by reductive amination to introduce the primary amine group. The final product has a molecular formula of C18H19N3O2 and a molecular weight of 323.36 g mol−1.

In vitro studies demonstrate that nivelon potently inhibits p38α kinase activity with an IC50 value of 48 nM. Cellular assays show that treatment of cultured fibroblasts with 1 µM nivelon reduces the production of pro‑inflammatory cytokines such as IL‑6 and TNF‑α following stimulation with lipopolysaccharide. The compound exhibits a favorable ADME profile in rodents, with oral bioavailability of approximately 62 % and a plasma half‑life of 4.3 h. Toxicity studies in rats indicate a maximum tolerated dose greater than 200 mg kg−1 per day, with no observable adverse effects on liver or kidney function.

Initial preclinical efficacy trials in a murine model of chronic obstructive pulmonary disease show that oral administration of nivelon at 10 mg kg−1 per day reduces airway inflammation and improves lung function parameters. These findings suggest potential therapeutic utility of nivelon for treating inflammatory diseases, pending further investigation in clinical trials.