KRN5

KRN5, a derivative of KRN2, is an oral active Nuclear factor of activated T cells 5 (NFAT5) suppressor, with an IC₅₀ of 750 nM. KRN5 has potential to treat NFAT5-mediated Chronic Arthritis^[1]. IC50 & Target: IC50: 750 nM (NFAT5)^[1]. In Vitro: KRN5 is less toxic than BBR as determined by a cytotoxicity assay, hERG K+ channel assay, cytochrome inhibition assay, and liver microsomal metabolic stability test, which makes it a potential drug candidate^[1].
KRN5 at a concentration of 1 μM inhibits the expressions of NFAT5, IL-6,MCP-1, and GM-CSF,which are NFAT5 target molecules, in RAW264.7 macrophages stimulated with LPS^[1].
In Vivo: Oral feeding of KRN5 (15 mg/kg and 60 mg/kg) every other day for 3 weeks from day 21 dose-dependently mitigates arthritis severity^[1].
The concentration of serum anti-type II collagen IgG also significantly decreases in the sera of KRN5-treated mice. TNF-α and IL-6 production by LPS-stimulated splenocytes are significantly lower in KRN5-treated CIA mice than in vehicle-treated mice^[1].