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Complement System

The complement system is a sophisticated part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promotes inflammation, and attacks the pathogen's cell membrane. This system is named for its capacity to "complement" the killing of pathogens by antibodies.

Comprising over 30 small proteins produced by the liver, the complement system circulates in the blood serum and within tissues throughout the body. These proteins are normally inactive but become sequentially activated in response to a pathogen. Activation can occur via three pathways: the classical pathway, which is triggered by antibodies bound to a pathogen; the lectin pathway, which is activated by mannose-binding lectin attaching to the pathogen surface; and the alternative pathway, which can be initiated directly by pathogen surfaces.

Each pathway leads to the cleavage of the protein C3, generating C3a and C3b fragments. C3b binds to the pathogen surface and can lead to direct opsonization—tagging the pathogen for destruction by phagocytes. C3a, along with other small fragments released during complement activation, acts as a chemoattractant to recruit immune cells to the site of infection and promote inflammation.

The final common step of the complement activation pathways is the assembly of the membrane attack complex (MAC). This complex forms a pore in the membrane of the target cell, leading to cell lysis and death. The MAC is particularly effective against gram-negative bacteria.

Regulation of the complement system is crucial, as overactivation can damage host cells. Regulators are present in blood plasma and on cell surfaces, ensuring the system is directed only at pathogens or damaged cells.

The complement system plays a crucial role not only in innate immunity but also as a bridge to adaptive immunity. It assists in clearing immune complexes and apoptotic cells, and in enhancing the humoral response and immune memory.

Understanding and manipulating the complement system has therapeutic potential for numerous diseases, including those that involve excessive or inappropriate activation of the complement pathways.

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  1. A35219
    Refinicopan

    Complement Factor D Inhibitor

    Refinicopan is a selective inhibitor of complement factor D, demonstrating an IC50 of 10 nM. This compound effectively inhibits rabbit erythrocyte hemolysis with an IC50 of 41 nM, indicating its capacity to modulate complement-mediated processes. Refinicopan's favorable pharmacokinetic and pharmacodynamic properties make it a valuable tool for investigating complement-related disorders and potential therapeutic interventions.
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  2. A35225
    Vensobafusp alfa

    Complement Protein C5 Inhibitor

    Vensobafusp alfa is a fusion protein that targets complement protein C5, functioning as a potent inhibitor. It combines an IgG4 monoclonal antibody directed against C5 with the complement factor H 1-5 domain, demonstrating significant anti-inflammatory and immunomodulatory properties. This reagent is applicable in the study of complement-mediated pathologies and therapeutic strategies targeting inflammatory conditions.
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  3. A35228
    3-O-(2'E,4'Z-Decadienoyl)ingenol

    Anticomplement Agent

    3-O-(2'E,4'Z-Decadienoyl)ingenol is a natural diterpene that functions as an anticomplement agent, demonstrating significant inhibitory activity with an IC50 of 89.5 μM. This compound is primarily utilized in research applications focused on complement system modulation and potential therapeutic interventions related to autoimmune conditions and inflammation. Its unique mechanism of action offers valuable insights into complement-related pathways in various biological contexts.
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  4. A35229
    Cevolisiran

    Complement component 3 (C3) synthesis reducer

    Cevolisiran is a small interfering RNA (siRNA) that specifically targets and reduces the synthesis of complement component 3 (C3). This reduction in C3 levels may modulate the complement pathway, which is pivotal in immune responses and inflammation. Cevolisiran is primarily used in research applications aimed at understanding the role of the complement system in various diseases and therapeutic strategies.
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  5. A35230
    Bisphenol A bissulfate disodium

    Complement System Inhibitor

    Bisphenol A bissulfate disodium is a complement system inhibitor with a significant role in modulating immune responses. This compound exhibits complement-inhibiting activity, demonstrating an IC50 value of 247 μM. It is utilized in research applications aimed at understanding the complement pathway and its implications in various diseases, making it a valuable tool in immunological studies.
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  6. A35231
    Bisphenol S disulfate disodium

    Complement inhibitor

    Bisphenol S disulfate disodium is a complement inhibitor that exhibits a half-maximal inhibitory concentration (IC50) of 660 μM. This compound is utilized in research applications aiming to explore complement-mediated pathways and their roles in various biological processes and diseases. Its ability to modulate complement activity makes it a valuable tool for studies involving immune response and inflammation.
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