C9 Inhibitors

The class of chemicals known as C9 inhibitors, when referring to complement component 9, consists primarily of compounds that target other components of the complement cascade. These inhibitors can prevent the assembly of the membrane attack complex by stabilizing or deactivating earlier components of the pathway such as C3 or C5. Their mode of action is largely based on binding to target molecules within the complement system, preventing their activation or interaction with other components necessary for the downstream formation of the C9-containing membrane attack complex.

Many C9 inhibitors operate by binding to C5, a precursor in the complement pathway necessary for C9 activation. The binding of these inhibitors to C5 prevents its cleavage into C5a and C5b, the latter of which is essential for the polymerization of C9 and the formation of the pore-like structure that disrupts cell membranes. Some inhibitors work upstream by preventing the formation or stabilization of C3 convertase (e.g., Compstatin), which is essential for the amplification of the complement cascade leading to C9 activation. Others increase the degradation of C3b or prevent the formation of the C5 convertases. These mechanisms ensure that C9 is not recruited to the cell surface and that the membrane attack complex is not formed, thus inhibiting the lytic function of C9.