complement

Complement C5-IN-1 is a small-molecule inhibitor of complement component 5 protein (C5).

Complement factor D-IN-1 is an effective and selective small-molecule reversible factor d inhibitor (IC50s: 0.006 and 0.05 μM in FD Thioesterolytic Fluorescent Assay and a MAC Deposition Assay, respectively).

Complement factor I, a serine protease, attenuates complement activity both in the fluid phase and on cell surfaces, working alongside cofactors such as factor H (FH), complement receptor 1 (CR1/CD35), C4 binding protein (C4BP), or membrane cofactor protein (MCP/CD46) [1].

Complement C1s-IN-1 is a potent and selective C1s inhibitor that is orally active and capable of crossing the blood-brain barrier, demonstrating an IC50 value of 36 nM [1].

Complement factor D-IN-2 is an inhibitor of Complement factor D and reduces the excessive activation of complement factor D.

C3a 70-77 2TFA(63555-63-5(free base)) (Complement 3a (70-77)) is an octapeptide corresponding to the COOH terminus of C3a.

C3a (70-77) is an octapeptide corresponding to the COOH terminus of C3a.

C3a Receptor Agonist (C3a receptor agonist 1) binds the G protein-coupled C3a receptors (C3aRs) in the immune system complement pathway. Activation of C3aR prevents neutrophils from being mobilized in a model of intestinal ischemia-reperfusion injury. C3aRs are expressed on neural progenitor cells and immature neurons in adult mice. C3a stimulates differentiation of neural progenitor cells in vitro.

C3a (70-77) TFA (Complement 3a (70-77) TFA) is a COOH-terminal fragment of the C3a anaphylatoxin peptide.

ADH-503 (GB1275) is a potent agonist of the integrin CD11b to mitigate myeloid cell immunosuppression.

Dexamethasone (Hexadecadrol) is a glucocorticoid receptor agonist and an IL receptor modulator. Dexamethasone has anti-inflammatory and immunosuppressive activity and induces autophagy. Dexamethasone inhibits LPS-induced inflammatory responses in macrophages.

Cyclosporin A is a naturally occurring cyclic polypeptide that is the active metabolite of a fungus. Cyclosporin A is an immunosuppressant that binds to procyclins and inhibits calcineurin (IC50=7 nM).

TLQP 21 acetate is a potent agonist of G-protein-coupled receptor complement-3a receptor 1 (C3aR1). The EC50 values are 10.3 μM for mouse and 68.8 μM for human. TLQP 21 acetate is a VGF-derived peptide with endocrine and extraendocrine properties.

PMX 205 acetate is an antagonist of complement C5a receptor (C5aR; CD88).

W-54011 is a potent non-peptide C5a receptor antagonist. W-54011 inhibits the binding of 125I-labeled C5a to human neutrophils (Ki: 2.2 nM). W-54011 inhibits C5a-induced intracellular Ca2+ mobilization, chemotaxis, and generation of ROS in human neutrophi

Lorukafusp alfa (14.18 mAb; hu14.18-IL2) is an immunocytokine composed of the humanized 14.18 anti-GD2 monoclonal antibody (mAb) connected to interleukin-2 (IL210). It exerts its anti-tumor effects [1] through the induction of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity. This is achieved by the targeted binding of hu14.18-IL2 to GD2-expressing tumor cells, which facilitates subsequent interaction with Fc receptors on immune effector cells, as well as the stimulation of natural killer (NK) and T cells through their IL2 receptors.

Activated C Subunit is utilized in synthesizing exon jumping oligomer conjugates that complement specific target sites within the human anti-muscular atrophy protein gene to promote exon 51 skipping, offering a research avenue for muscular dystrophy [1].

PMX 205 Trifluoroacetate is a potent complement antagonist of C5a receptor.

3β-(Acetyloxy)stigmast-5-en-7-one exhibits anti-complement activity [1].

Chrysoeriol-7-O-glucoside can strongly inhibit the classical pathway of the complement system.Chrysoeriol-7-O-d-glucoside and luteolin-7-O-d-glucoside can inhibit palmitic acid uptake into small intestinal brush border membrane, apigenin-7-O-d-glucoside can inhibit alpha-amylase activity; they can enhance norepinephrine-induced lipolysis in fat cells.

3-Phenoxybenzaldehyde is a complement (classical pathway) inhibitor with IC50 of 1388μM.

POT-4 acetate inhibits Complement C3 activation. POT-4 acetate can be used for studies about age-related macular degeneration.

Val-Gly-Ser-Glu (NSC 350591), an ECF-A tetrapeptide, dose-dependently enhances the rosetting of human eosinophils with complement-coated sheep erythrocytes (EAC3b) without affecting neutrophils [1].

C5aR1 antagonist peptide, a biologically active linear peptide originating from the C-terminus of the chemokine complement fragment 5 anaphylatoxin (C5a), inhibits C5a binding and activity at human and rat C5a receptors. Overexpression of C5a is linked to various immunoinflammatory diseases, including arthritis, Alzheimer’s disease, cystic fibrosis, and systemic lupus erythematosus.

Campneoside II, a compound extracted from the wood of Paulownia tomentosa var. tomentosa, demonstrates remarkable anti-complement activity [1].

Avacincaptad pegol, a pegylated aptamer, stands out as an effective C5 complement inhibitor capable of mitigating inflammation-induced damage to the retinal pigment epithelium (RPE). This compound is under investigation for its potential application in treating Stargardt macular dystrophy (STGD1) and geographic atrophy (GA) [1] [2].

Anionic interaction of Beta-amyloid (1-11) with Factor XII is suspected to cause massive activation of the C4 (complement 4) system in the cerebrospinal fluid of Alzheimer’s disease patients.

PMX 205 is an effective complement antagonist of the C5a receptor.

JPE-1375, a complement C5a receptor 1 (C5aR1) antagonist, effectively inhibits polymorphonuclear leukocyte mobilization (EC50=6.9 µM) and reduces TNF levels (EC50=4.5 µM) in mice, making it useful for autoimmune and inflammatory disease research [1].

C5a Receptor Agonist (mouse, human) is a bioactive peptide derived from the C-terminus of the complement fragment 5 anaphylatoxin (C5a), functioning as an agonist for the C5a receptor. This peptide plays a role in mediating inflammatory responses by promoting chemotaxis, leukocyte degranulation, enhanced vascular permeability, and cytokine production. Its agonistic activity is critically dependent on the presence of cyclohexylalanine at position 5 and the d-isomer of Arg at the terminal position.

Gavilimomab (ABX-CBL), an IgM murine monoclonal antibody, targets CD147 on cell surfaces to induce complement-mediated cytotoxicity. It is utilized in the study of graft-versus-host disease (GVHD) [1].

Empasiprubart (ARGX-117) is a humanized inhibitory monoclonal antibody targeting complement C2. It inhibits the formation of C3 proconvertase, obstructing classical and lectin pathway activation by binding to the Sushi-2 domain of C2 upstream of C3. The binding of Empasiprubart is pH- and calcium-dependent. The compound demonstrates efficacy in preventing complement-mediated cytotoxicity within in vitro models of autoimmune hemolytic anemia and antibody-mediated organ transplant rejection [1].

AMY-101 is a peptidic inhibitor of the central complement component C3 (KD: 0.5 nM). AMY-101 shows a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation.

Avacincaptad pegol (ARC1905), an anti-C5 RNA aptamer, prevents the cleavage of complement factor 5 (C5) into fragments C5a and C5b. It is currently under investigation for the treatment of age-related macular degeneration (AMD).

PMX-53, a macrocyclic complement 5a (C5a) peptidomimetic and C5a receptor antagonist (IC50 = 0.3 µM), effectively inhibits the C5a-induced secretion of myeloperoxidase (MPO) in isolated human polymorphonuclear leukocytes (PMNs). Administered orally at 10 mg/kg, PMX-53 mitigates vascular leakage, PMN infiltration, and the production of TNF-α and IL-6 in a rat peritoneal Arthus reaction model. Additionally, in a 3-nitropropionic acid (3-NP)-induced Huntington’s disease rat model, it alleviates body weight loss, anorexia, and striatal degeneration. Furthermore, at a dose of 3 mg/kg, PMX-53 decreases atherosclerotic lesion size and lipid content in ApoE-/- mice.

Versicolactone B, a sesquiterpene extracted from Viola yedoensis, exhibits anti-complement activity affecting both the classical and alternative pathways [1].

Zilucoplan (RA101495), a 15-amino acid macrocyclic peptide and potent complement component 5 (C5) inhibitor, is utilized in the study of immune-mediated necrotising myopathy (IMNM) [1] [2].

Ravulizumab (ALXN1210) is a humanized monoclonal antibody targeting complement factor 5 that specifically binds to human complement protein C5 with high affinity to block complement activation. Ravulizumab can be used for the prevention and treatment of paroxysmal sleep hemoglobinuria, atypical hemolytic uremic syndrome and myasthenia gravis.

PMX-205 is a cyclic hexapeptide that acts as a potent antagonist of C5a receptor (C5aR; IC50= 31 nM).1It is orally active and blocks inflammatory signaling and symptoms in animal models of colitis and allergic asthma.2,3PMX-205 is also brain penetrant and reduces neuroinflammation and neurodegeneration in an animal model of Alzheimer's disease.4 1.March, D.R., Proctor, L.M., Stoermer, M.J., et al.Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activityMol. Pharmacol.65(4)868-879(2004) 2.Jain, U., Woodruff, T.M., and Stadnyk, A.W.The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10Br. J. Pharmacol.168(2)488-501(2013) 3.Staab, E.B., Sanderson, S.D., Wells, S.M., et al.Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthmaInt. Immunopharmacol.21(2)293-300(2014) 4.Fonseca, M.I., Ager, R.R., Chu, S.-H., et al.Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's diseaseJ. Immunol.183(2)1375-1383(2009)

AMY-101 TFA (Cp40 TFA) is a peptidic inhibitor of the central complement component C3 (KD: 0.5 nM). AMY-101 TFA shows a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation.

Apigenin-4'-O-rhamnosylglucoside can strongly inhibit the classical pathway of the complement system.

Pelecopan (BCX9930) is a potent, selective, orally active inhibitor of complement factor D (IC50= 14.3 nM). Pelecopan can prevent both intravascular and extravascular hemolysis in PNH.

Cemdisiran, an investigational N-acetylgalactosamine-conjugated RNAi (RNA interference) agent with terminal sugar modification, is a small interfering RNA (siRNA) designed to specifically target and suppress the C5 mRNA, thereby reducing the liver's production of the complement component C5 [1].

ARC186 is a highly potent aptamer that serves as a complement inhibitor by blocking the convertase-catalyzed activation of C5.

WKYMVM-NH2 TFA, a potent agonist for N-formyl peptide receptor (FPR1) and FPRL1/2, activates key leukocyte effector functions including chemotaxis, complement receptor-3 mobilization, and NADPH oxidase activation, as documented in references [1] [2] [3].

Lampalizumab (RG 7417), a humanized monoclonal antibody, selectively inhibits complement Factor D in the alternative complement pathway by binding to an exosite and sterically hindering Factor B's access to the active site. It is employed in the study of age-related macular degeneration (AMD) [1] [2].

Gefurulimab (ALXN-1720) is a bispecific antibody derived from humans, targeting complement C5 and albumin. It specifically binds to C5, inhibiting its activation [1].

Crovalimab (SKY59; RO7112689) is a novel humanized antibody designed to target C5 in a pH-dependent manner, demonstrating binding affinities (KD) of 15.2 nM and 16.8 μM at pH levels of 7.4 and 5.8, respectively. Additionally, it shows high affinity for human FcRn at pH 6.0, with a KD of 17 μM. By blocking C5 cleavage by C5 convertase and inhibiting the activity of a C5 variant (p.Arg885His), Crovalimab effectively prevents the formation of C5b-9 across the classical (CP), lectin (LP), and alternative (AP) complement pathways. This characteristic highlights its potential utility in research concerning paroxysmal nocturnal hemoglobinuria (PNH) and other complement-mediated diseases.

Olendalizumab (ALXN1007), a humanized IgG2-G4-κ antibody derived from mice, specifically targets Complement protein C5a with a binding affinity (K i) of 60 pM. This compound is designed to inhibit the complement inflammatory pathway. Additionally, olendalizumab is utilized in the research of complement-mediated disorders triggered by the coronavirus [1] [2].

Factor B-IN-3 is a potent inhibitor of complement factor B. Factor B-IN-3 can be used to study inflammatory and immune-related diseases.