Complement function or activity test allows for the determination of whether the protein is present and whether it has normal functional activity. A wide range of assays are now available in Creative Biolabs, such as Hemolysis assays (CH50 or AH50), Elisa Assays (c3a, c5a, FH, FB, C5b-9 or others), Complement Inhibitor Validation (IC50)......
The technical experts of Creative Biolabs are looking forward to providing a high-quality and high-efficiency soluble complement regulators development service to your project needs.
Complement is a central element of innate immunity and this vital defense system initiates and coordinates immediate immune reactions which attack and eliminate microbes, foreign particles, and altered self-cells. Newly generated activation products are extremely toxic and consequently, activation is highly restricted in terms of time and space. The past few years have been proven to be a highly successful and exciting period for the field of complement-directed drug discovery and development. Driven by promising experiences with the first marketed complement drug, increased knowledge about the involvement of complement in health and disease, the field has been a surge in creative approaches to therapeutically intervene at various stages of the cascade.
Our body produces a natural panel of highly effective complement inhibitors that primarily act at the level of convertases or the TCC, and which can be exploited for therapeutic purposes. With the strongest activity on both classical pathway (CP) and alternative pathway (AP) mediated complement activations, soluble CR1 (sCR1, TP10, Avant) has been the most extensively developed regulator of complement activation and used in a variety of disease models. In addition, recombinant FH has been evaluated for use in AMD and renal diseases that are often affected by polymorphisms in the FH gene. Early examples in clinical development include the combination of the short four CCP-domain regulators MCP and DAF into an inhibitor with extended regulatory functions (CAB-2, Millenium) or the truncation of CR1 into shorter fragments.
Fig.1 Modular Concept of Complement Regulators and Receptors Composed of CCP Domains and Their Use for Designing Therapeutic Complement Inhibitors.
Rely on Creative Biolabs’ experienced team, we have developed an advanced platform of Soluble Complement Regulators services to support your projects of sCR1 and CAB-2. We will carry out your experiments using optimized and validated protocols. More than that, our soluble complement regulators services can be tailor-designed to meet your specific needs and it is fast, reliable and affordable. Our services including but not limited to:
Because regulators of complement activation are natural modifiers of complement activities and prevent a host cell from attack by its own defense system, they have been considered for therapeutic use since the early stages of complement drug discovery. A first breakthrough was reached with the expression of a soluble form of complement receptor 1 (sCR1) 53. sCR1 showed promising results in the treatment of I/R injury and various other conditions in experimental animal models. Based on these results, sCR1 was developed as a therapeutic (TP10, Avant Immunotherapeutics) for use after coronary artery bypass graft surgery.
A number of promising approaches for the clinical substitution, inhibition or modulation of complement have been developed and are presented in the following section. Soluble forms of MCP, DAF, and CD59 have also been considered as therapeutics. Whereas DAF and MCP each offer only a single regulatory activity, a recombinant chimera of their extracellular parts have been developed. The resulting sDAF-sMCP hybrid was initially named “complement activity blocker 2” (CBA-2/MLN-2222, Millenium Pharmaceuticals).
C4b-binding protein (C4BP) acts as a regulatory protein mainly involved in the classical and the lectin pathways, where it serves as a functional cofactor in factor I-mediated cleavage of C4b and C3b and accelerates decay of C3-convertase. Now, it has become an important target for therapy exploration to regulate the complement activation.
Factor H (FH) acts as a deactivator of complement system, and it is essential for regulating the alternative pathway (AP) in blood and on cell surfaces. FH deficiency will induce increased complement activity on healthy host cells, resulting in autoimmune diseases. Therefore, FH has become a promising and effective target for therapeutic antibody exploration and clinical trial.
Factor I (FI), also known as C3b/C4b inactivator, is a serine proteinase that is essential for regulating the complement cascade. It can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes, decreasing the activation of the complement system. FI dysregulation or deficiency is closely associated with various clinical implications. Now, it has been a promising and effective target for the treatment of diseases associated with abnormal or loss of complement control.
If you are interested in our soluble complement regulators services to support your program, please contact us for more details. Based on the quality and quantity requirement of your request, a formal quote will be sent back to you for your review, comment, and/or acceptance.