Complement Inhibitor Validation

Creative Biolabs is one of the well-recognized expert professionals in the field of complement therapeutics and related services. Our technical experts are looking forward to offering high-quality and custom complement inhibitor validation services for our clients.

Complement Inhibitor Overview

The complement system is a cascade reaction playing a pivotal function in recognition and eliminating of invading pathogens, which serves as a regulator of multiple human diseases. About 40 components (proteins and enzymes) form the complement cascade, all of which are indispensable and tightly coordinate with each other to play a normal complement activity. Some of these components positively regulate the complement system so that the complement cascade can be activated to function properly, whereas, others act as inhibitors to regulate the complement system in a negative way to prevent its spontaneous or over-activation.

Until now, a diversity of complement inhibitors has been described, including natural proteins in the complement system and those developed by biotechnology. Complement factor I (CFI), complement factor H (CFH), C4 binding protein (C4BP), decay-accelerating factor (DAF), CD35 (CR1), membrane cofactor protein (MCP), etc., are natural inhibitors regulating complement pathways in different ways. Several complement inhibitors have been approved by Food and Drug Administration (FDA) for the treatment of related diseases, including Eculizumab (anti-C5 monoclonal antibody), Berinert, and Cinryze (both are C1 esterase inhibitor).

Fig. 1 Complement system and its targeted modulation. (Yarmoska et al., 2021)

Fig. 1 Complement system and its targeted modulation.1

Complement Inhibitor Validation Services

As the revealing of the relationship between the complement system and diseases, increasing complement inhibitors are currently developed and evaluated in clinical trials for the related disease therapy. Therefore, complement inhibition test or complement inhibitor validation is necessary to measure the effect of complement inhibitors.

As an experienced expert in complement therapeutics, Creative Biolabs provides comprehensive custom validation services for the efficient identification of potential complement inhibitors. Based on the principle of combining the individual component activity test with the whole complement cascade activity assessment, our scientists verify or screen complement inhibitors mainly through the following approaches:

  1. Hemolytic inhibition assay: for validation of both individual inhibition and total complement activity inhibition assessment;
  2. Cell imaging-based high-throughput screening: for fast and efficient screening potential complement inhibitors on a large scale;
  3. Immunochemical assays for individual components determination: mainly for individual component determination, such as immunoprecipitation (IP), enzyme-linked immunosorbent assay (ELISA), radial immunodiffusion (RID). This method also can be used to measure complement autoantibodies.
  4. Receptor ligand binding assay: for complement receptor binding inhibition mainly by competition ELISA, other sensitive binding tests are also available if the ligand-receptor samples are purified.
  5. Quantitative chromogenic assays: for C1 inhibitor activity evaluation.

With over a decade of experience and the state-of-the-art drug development platforms, Creative Biolabs provides highly custom solutions for complement inhibitors validation to effectively support your anti-complement therapeutics development.

If you are interested, please directly contact us for more information.

Reference

  1. Yarmoska, Steven K., et al. "Modulation of the complement system by neoplastic disease of the central nervous system." Frontiers in Immunology 12 (2021): 689435.

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Questions & Answer

A: Complement inhibitor validation typically involves several steps, including: (a) In vitro Testing: Assessing the inhibitor's effect on complement activation in controlled cell-based assays or plasma samples. (b) In vivo Studies: Evaluating the inhibitor's impact in animal models, measuring complement inhibition and potential therapeutic effects. (c) Pharmacokinetics (PK) and Pharmacodynamics (PD): Determining how the inhibitor is absorbed, distributed, metabolized, and excreted, as well as its impact on complement activity. (d)Toxicity and Safety Assessment: Investigating potential adverse effects, such as immunogenicity or interference with other physiological processes. (e) Clinical Trials: Conducting controlled human trials to validate safety, efficacy, and dosing regimens.

A: Yes, complement inhibitor validation can be tailored to specific diseases. The choice of assays, models, and endpoints may vary based on the disease's underlying mechanisms and manifestations. Personalized validation approaches may enhance the inhibitor's effectiveness and safety for a particular condition.

A: Technologies, such as high-throughput screening, advanced imaging techniques, and single-cell analysis, have improved the precision and efficiency of complement inhibitor validation. These technologies allow researchers to study complement dynamics at a finer resolution, enabling more accurate assessments of the inhibitor's effects.

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