Description

Product Description

Zilucoplan TFA (RA101495) is a synthetic, macrocyclic peptide designed as a potent and selective inhibitor of complement component 5 (C5), a terminal protein in the classical complement pathway. By binding to C5 with high affinity, Zilucoplan TFA prevents its enzymatic cleavage into C5a and C5b, thereby inhibiting the formation of the membrane attack complex (MAC, C5b-9).

This inhibitory effect on the complement cascade is of particular interest for the study of autoimmune diseases, neuromuscular disorders, and inflammatory pathologies characterized by excessive complement activation. Researchers have used Zilucoplan TFA as a reference compound in studying complement-mediated cytotoxicity, as well as in modeling complement-dependent tissue injury.

Structure and Physicochemical Features

Zilucoplan TFA is a 15–amino acid macrocyclic peptide that integrates both natural and non-natural amino acids to enhance stability, receptor selectivity, and in vivo half-life. The macrocyclic structure confers exceptional protease resistance and enhanced plasma retention, making it suitable for long-term mechanistic research. The trifluoroacetate (TFA) salt form ensures high purity, improved solubility, and consistent analytical reproducibility.

Biological and Research Relevance

The complement system is a crucial component of innate immunity, mediating host defense and inflammatory responses. Dysregulation of complement activation can lead to tissue destruction, autoimmunity, and chronic inflammation. Zilucoplan TFA specifically targets the C5 cleavage event, which represents the final common pathway leading to membrane attack complex formation.

Inhibition of this pathway has shown protective effects in models of myasthenia gravis, immune-mediated necrotizing myopathy, paroxysmal nocturnal hemoglobinuria (PNH), and complement-associated neuropathies. In preclinical research, Zilucoplan demonstrates rapid onset of C5 blockade, sustained complement inhibition, and dose-dependent modulation of complement activity markers such as CH50 and C5b-9 complex formation.

Experimental Applications

Zilucoplan TFA is utilized in a broad range of in vitro and in vivo experimental systems, including:

• Complement-mediated cytotoxicity assays to quantify MAC-dependent cell lysis.

• Autoimmune disease models, particularly those involving antibody-mediated complement activation.

• Neuromuscular junction studies, to evaluate complement contribution to muscle fiber necrosis.

• Inflammation research, exploring the cross-talk between complement activation and cytokine release.

Zilucoplan’s mechanism-based inhibition provides researchers with a powerful tool for dissecting complement-driven pathophysiology and evaluating new therapeutic strategies aimed at complement regulation.

Product Specifications

Mechanism of Action

Zilucoplan TFA acts as a selective complement component 5 (C5) inhibitor, directly preventing the proteolytic cleavage of C5 into its two active fragments, C5a and C5b. Normally, C5a functions as a potent anaphylatoxin, triggering inflammation and leukocyte activation, while C5b initiates assembly of the membrane attack complex (MAC, C5b-9), leading to cell lysis.

By blocking C5 cleavage, Zilucoplan effectively halts both downstream inflammatory signaling and cytolytic activity. This dual blockade provides comprehensive control over complement-mediated injury pathways, making it a cornerstone tool in complement biology research.

Mechanistically, the peptide binds to a conserved site on the C5 molecule, sterically hindering the access of convertase enzymes (C5 convertase). The result is reduced deposition of MAC on cell membranes, lower inflammatory cytokine release, and protection against complement-dependent tissue damage.

Because complement activation contributes to pathology in a wide range of diseases—from autoimmune neuromuscular syndromes to renal and vascular inflammation—Zilucoplan TFA provides a unique, selective means to dissect complement signaling without affecting upstream immune recognition processes.

Side Effects

In research contexts, Zilucoplan TFA has been found to be well-tolerated and highly specific for its target. However, inhibition of complement activity may increase susceptibility to bacterial infection in in vivo studies, particularly with Neisseria species, due to impaired MAC formation.

Common laboratory observations may include:

• Reduced complement activity markers (CH50, C5b-9)

• Altered inflammatory cytokine expression profiles

• No cytotoxicity or nonspecific binding in cell culture models

Researchers should handle Zilucoplan TFA using appropriate protective measures and maintain aseptic conditions to avoid contamination or degradation.

Keywords

Zilucoplan TFA, RA101495, complement C5 inhibitor, macrocyclic peptide, immune-mediated necrotizing myopathy, complement blockade, MAC formation inhibitor, complement pathway peptideWhat is Zilucoplan TFA?, immunology research compound, autoimmune disorder peptide

Shipping Guarantee

All shipments are handled using validated cold-chain logistics to preserve peptide integrity. Each package is sealed in moisture-proof containers with secondary protective wrapping and continuous temperature monitoring. Products are shipped via express international couriers with full tracking and insurance coverage.

Trade Assurance

We ensure product authenticity, verified ≥99% purity, and compliance with analytical standards (HPLC, MS, and NMR). Each batch is supplied with a Certificate of Analysis (CoA). Our trade assurance policy guarantees replacement or refund for any deviation from listed specifications.

Payment Support

We provide flexible and secure global payment options to support international research transactions. Accepted payment methods include PayPal, major credit cards (Visa, MasterCard, American Express), telegraphic transfer (T/T), and cryptocurrencies (USDT, Bitcoin, Ethereum). All transactions are protected by industry-standard encryption and verified payment gateways to ensure confidentiality and fund security.