Complement System Inhibitor

Crovalimab (SKY59; RO7112689) is a novel humanized antibody against C5 in a pH-dependent manner with KDs of 15.2 nM and 16.8 μM at pH 7.4 and 5.8, respectively. Crovalimab binds human FcRn with great affinity (KD: 17 μM at pH 6.0). Crovalimab can block cleavage of C5 by the C5 convertase and inhibite the activity of a C5 variant (p.Arg885His). Crovalimab inhibits C5b-9 formation significantly in all three complement pathways, the classical pathway (CP), lectin pathway (LP), and alternative pathway (AP). Crovalimab has the potential for paroxysmal nocturnal hemoglobinuria (PNH) and complement-mediated diseases research.

Riliprubart (SAR 445088) is a selective anti-C1s humanized IgG4 monoclonal antibody with mutations that enhance its binding to the neonatal Fc receptor. Riliprubart blocks activation of the classical complement pathway, prevents the formation of the C3 convertase C4b2a, and inhibits complement-mediated hemolytic activity. Riliprubart can be used in research related to classical complement-mediated diseases, cold agglutinin disease, and chronic inflammatory demyelinating polyneuropathy. For the isotype control of Riliprubart, refer to Human IgG4 (S228P) kappa, Isotype Control (HY-P99003).

EG01377 dihydrochloride is a potent, bioavailable and selective inhibitor of neuropilin-1 (NRP1), with a K_d of 1.32 μM, and IC₅₀s of 609 nM for both NRP1-a1 and NRP1-b1. EG01377 dihydrochloride has antiangiogenic, antimigratory, and antitumor effects.

Iptacopan (LNP023) hydrochloride is an effective and orally-active highly selective factor B inhibitor with an IC₅₀ value of 10 nM and K_D of 7.9 nM. Iptacopan hydrochloride exerts a proximal effect in the complement cascade reaction, preventing the destruction (hemolysis) of red blood cells in PNH and the damage of renal cells in IgAN and C3G. Iptacopan hydrochloride can be used for the study of complement-mediated diseases, particularly paroxysmal nocturnal hemoglobinuria (PNH), primary immunoglobulin A nephropathy (IgAN), and complement 3 glomerulopathy (C3G).

Zilucoplan (RA101495), a 15-amino acid macrocyclic peptide, is a potent complement component 5 (C5) inhibitor. Zilucoplan can be used in research of immune-mediated necrotising myopathy (IMNM).

Cyclosporin A (Standard) (Cyclosporine A (Standard)) is the analytical standard of Cyclosporin A (HY-B0579). This product is intended for research and analytical applications. Cyclosporin A (Cyclosporine A) is an immunosuppressant which binds to the cyclophilin and inhibits phosphatase activity of protein phosphatase 2B (PP2B/calcineurin) with an IC₅₀ of 5 nM. Cyclosporin A is a molecular glue, binds to cyclophilin and calcineurin, leading to inactivation of nuclear Factor of activated T Cells (NFAT) and a subsequent decrease in the immune response. Cyclosporin A also inhibits CD11a/CD18 adhesion.

N-Acetylserine (N-Acetyl-L-serine) is a complement pathway modulator targeting activated third complement protein (C3b) and an amino-terminal residue (an N-terminal acetylation modification group). N-Acetylserine reacts with the exposed thioester group of C3b via its hydroxyl group, thereby blocking the covalent binding of glycerol to this thioester group. N-Acetylserine widely exists in soluble proteins of mammalian cells (accounting for approximately 80% of such proteins). N-Acetylserine has a blocking property that prevents direct Edman sequencing of proteins; deblocking is achievable through trifluoroacetic acid-catalyzed N→O acetyl migration followed by β-elimination. N-Acetylserine is suitable for sequencing of proteins with N-terminal acetylserine modification.

Vilobelimab (CaCP-29, IFX-1) is a monoclonal anti-C5a antibody to the allergen C5a, a pro-inflammatory complement division product that plays a central role in mediating organ dysfunction. Vilobelimab acts as a C5a inhibitor, inhibiting neutrophil activation, chemotaxis, and reducing inflammatory signalling, and may be used in studies related to sepsis, COVID-19, etc.

Avdoralimab (IPH 5401) is a fully human IgGκ monoclonal antibody that targets the complement C5a receptor 1 (C5aR1) that prevents its binding to C5a. Avdoralimab can be used for complement-driven inflammatory diseases and solid tumours research.

POT-4 (AL-78898A), a Compstatin derivative, is a potent inhibitor of complement factor C3 activation. POT-4 can be used for age-related macular degeneration research

Claseprubart (DNTH103) is an inhibitor targeting C1s of the complement system and an inhibitor of the C1 component of the complement cascade. Claseprubart is in phase 2 clinical evaluation. Claseprubart has application potential in research related to multifocal motor neuropathy and generalized myasthenia gravis.

BCX 1470 methanesulfonate inhibits the esterolytic activity of factor D (IC₅₀=96 nM) and C1s (IC₅₀=1.6 nM), 3.4- and 200-fold better, respectively, than that of trypsin.

Tesidolumab (LFG316) is a fully-human IgG1/λ anti-C5 monoclonal antibody of 143 kDa (without glycosylation). Tesidolumab (LFG316) blocks cleavage of C5 and prevents subsequent formation of the membrane attack complex.

Compound C5-IN-1 (Compound 7) is a selective allosteric inhibitor of complement component protein C5. Compound C5-IN-1 prevents C5 from being cleaved by C5 convertase, inhibits the cleavage of C5 into C5a and C5b, and thus blocks the formation of membrane attack complex (MAC). Compound C5-IN-1 has an IC₅₀ of 0.77 μM and 5 nM in 50% human whole blood and 2% human serum to block MAC deposition induced by zymosan, respectively. Compound C5-IN-1 can be used to study diseases related to complement overactivation, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

Cyclosporin A-d₄ (Cyclosporine A-d₄) is the deuterated-labeled Cyclosporin A (HY-B0579). Cyclosporin A (Cyclosporine A) is an immunosuppressant which binds to the cyclophilin and inhibits phosphatase activity of protein phosphatase 2B (PP2B/calcineurin) with an IC₅₀ of 5 nM. Cyclosporin A is a molecular glue, binds to cyclophilin and calcineurin, leading to inactivation of nuclear Factor of activated T Cells (NFAT) and a subsequent decrease in the immune response. Cyclosporin A also inhibits CD11a/CD18 adhesion.

Gefurulimab (ALXN-1720) is a high-affinity antibody inhibitor targeting complement protein C5, which can specifically bind to C5 and inhibit its cleavage into C5a and C5b. Gefurulimab can block the activation of the terminal complement pathway and reduce inflammatory damage. Gefurulimab can effectively reduce the formation of membrane attack complex (MAC) and has good pharmacokinetic properties. Gefurulimab can be used to study kidney and autoimmune diseases related to abnormal activation of the complement system, such as IgA nephropathy, lupus nephritis, and myasthenia gravis.

EG01377 is a potent, bioavailable and selective inhibitor of neuropilin-1 (NRP1), with a K_d of 1.32 μM, and IC₅₀s of both 609 nM for NRP1-a1 and NRP1-b1. EG01377 has antiangiogenic, antimigratory, and antitumor effects.

ATWLPPR Peptide TFA, a heptapeptide, acts as a selective neuropilin-1 inhibitor, inhibits VEGF₁₆₅ binding to NRP-1, used in the research of angiogenesis. ATWLPPR Peptide TFA has potential in reducing the early retinal damage caused by diabetes.

Vemircopan (ALXN2050) is an orally active complement factor D (FD) inhibitor. Vemircopan can be used in the research of diseases such as myasthenia gravis, lupus nephritis, IgA nephropathy, and paroxysmal nocturnal hemoglobinuria.

ANX-M1 is a blood-brain barrier-permeable anti-C1q antibody. ANX-M1 can slow down the progression of retinal degeneration following photo-oxidative damage. ANX-M1 has been incorporated into nanocarriers to evaluate its brain delivery efficacy in a mouse model of Alzheimer's disease. ANX-M1 is applicable for research on age-related macular degeneration and Alzheimer's disease ^[1].