denenicokin

Denenicokin (recombinant human interleukin-21, rIL-21, BMS-982470) is a recombinant wild-type form of the human cytokine interleukin-21 (IL-21). Originally developed by ZymoGenetics (later acquired by Bristol Myers Squibb), denenicokin acts as an immunostimulant by binding to the heterodimeric IL-21 receptor complex (comprising IL-21R and the common gamma chain, IL-2RG) on T cells, B cells, and natural killer (NK) cells. This binding activates downstream JAK/STAT signaling pathways (primarily JAK1, JAK3, STAT1, and STAT3), promoting the proliferation, differentiation, and cytolytic activity of cytotoxic CD8+ T cells and NK cells, while enhancing B-cell differentiation into plasma cells. Denenicokin was clinically evaluated in Phase I and Phase II trials for the treatment of metastatic melanoma, renal cell carcinoma, ovarian cancer, and other solid tumors, both as a monotherapy and in combination with checkpoint inhibitors like ipilimumab and nivolumab. However, its clinical development was discontinued due to its short half-life and limited efficacy as a monotherapy.

Other names

L-methionyl(human interleukin-21)recombinant human IL-21recombinant human interleukin-21rIL-21rIL21rIL 21wild-type IL-21wild-type interleukin-21