S100 calcium-binding protein A9 (S100A9) homodimer (S100A9 homodimer)

S100 calcium-binding protein A9 (S100A9) is a low-molecular-weight protein that belongs to the S100 family and is primarily expressed in neutrophils and monocytes (NIH, 2024; MDPI, 2012). While it predominantly forms a heterodimer with S100A8 known as calprotectin, S100A9 also exists as a homodimer, particularly under inflammatory conditions where it is stabilized by inflammatory stimuli (PLoS ONE, 2013; Frontiers, 2021). The S100A9 homodimer functions as a damage-associated molecular pattern (DAMP) or alarmin, signaling through receptors such as Toll-like receptor 4 (TLR4), the receptor for advanced glycation end products (RAGE), and EMMPRIN to trigger pro-inflammatory cascades including the NF-κB and MAPK pathways (MDPI, 2022; NIH, 2025). In the context of oncology, S100A9 is a key regulator of the recruitment and immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), which promotes tumor growth, survival, and metastasis (NIH, 2013; Scientific Reports, 2024). Consequently, the S100A9 homodimer has emerged as a significant therapeutic target, with small-molecule inhibitors like quinoline-3-carboxamides (e.g., tasquinimod and paquinimod) designed to block its receptor interactions (NIH, 2013; ASH, 2025). These drugs have shown promise in treating various cancers, such as prostate cancer and chronic lymphocytic leukemia, as well as autoimmune diseases like rheumatoid arthritis and lupus (NIH, 2025; ASH, 2025).

Other names

MRP14Calgranulin BP14CAGBCFAGL1AGLIAGMAC387Myeloid-related protein 14

Binding to the S100A9 homodimer to inhibit its interaction with pro-inflammatory receptors such as TLR4, RAGE, and EMMPRIN, thereby suppressing downstream NF-κB and MAPK signaling pathways (MDPI, 2022; NIH, 2025).