CCR3 is a chemokine receptor. CCR3 is abundant in eosinophils, mast cells, basophils, and human Th2-like T lymphocyte subsets β Chemokine receptor. Besides, CCR3 is an eotaxin receptor, but it also recognizes other chemokines, such as RANTES and macrophage inflammatory protein 1 α And monocyte chemoattractant proteins 2, -3, and -4. Moreover, CCR3 plays an important role in regulating eosinophil migration. Eosinophils are a group of leukocytes relevant to many inflammatory pathologies, including asthma. Furthermore, CCR3 binds to the CC chemokine eotaxin.
Meanwhile, CC chemokine receptors are integrated membrane proteins. They specifically bind to and respond to cytokines of the CC chemokine family. Nonetheless, CCR3 is a receptor for a variety of inflammatory/inducible CC chemokines. Importantly, CCR3 is important for the basal transport of eosinophils to the intestinal mucosa rather than the lung. The transport of activated eosinophils to sensitized lungs is mainly dependent on CCR3. Obviously, CCR3 disruption significantly reduced eosinophil recruitment to the lung after the allergen challenge. Interferon CCR3 up regulates neutrophil and monocyte-like U937 cells in vitro. Here, we will introduce an orally actively CCR3 inhibitor, ALK4290 (AKST4290).
ALK4290 (AKST4290) is an Orally Active CCR3 Inhibitor.
First of all, ALK4290 (AKST4290) is a potent and orally actively CCR3 inhibitor with a Ki of 3.2 nM for hCCR3. Particularly, ALK4290 has the potential for the research of nonvascular age-related macular degeneration and Parkinsonism.
In the second place, ALK4290 targets eotaxin, an immunomodulatory chemokine highly expressed in CNVs, choroidal endothelial cells, and circulation in AMD. Increased eotaxin and type 3 C-C chemokine receptors increase membrane permeability and degradation, immune cell recruitment, and disrupt regulation. In fact, CCR3 and its ligand CCL11 are in neovascular lesions. CCL11 levels are elevated in choroidal endothelial cells and systemic circulation in patients with AMD. Additionally, ALK4290 reduces inflammatory cytokines.
All in all, ALK4290 (AKST4290) is a potent and orally actively CCR3 inhibitor.