Chemical Approaches to Modulating Complement-Mediated Diseases

J Med Chem. 2018 Apr 26;61(8):3253-3276. doi: 10.1021/acs.jmedchem.7b00882. Epub 2017 Oct 18.


Numerous diseases are driven by chronic inflammation, placing major burdens on our health systems. Controlling inflammation is an important preventative and therapeutic goal. Over 40 "Complement" proteins are produced in blood or on cell surfaces through activation of the Complement protein network mainly by infection or injury. These proteins complement immune cells and antibodies to identify, tag, destroy, and eliminate pathogens and infected or damaged cells and repair tissues. If the inflammatory stimulus is not removed by localized acute immune responses, Complement activation may be prolonged or misdirected to healthy cells, and chronic inflammation can lead to inflammatory or autoimmune diseases. The formation, structures, and interplay between Complement proteins are complex, and this has limited our detailed understanding of their roles and importance in physiology and disease. With the availability of new structures for Complement proteins, new knowledge of how they function, and new modulators of Complement-driven signaling, there are also new opportunities to intervene in Complement-mediated disease. Small molecule and peptide-based drug leads, identified as clues for Complement-directed therapeutic development, are assembled here together with the available evidence for their efficacy in cellular and animal models of human inflammatory disease and in some human clinical conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Cell Line, Tumor
  • Complement Activation / drug effects*
  • Complement Activation / immunology
  • Complement Activation / physiology
  • Complement Inactivating Agents / therapeutic use*
  • Complement System Proteins / drug effects*
  • Complement System Proteins / immunology
  • Complement System Proteins / physiology
  • Humans


  • Complement Inactivating Agents
  • Complement System Proteins