complement system

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).

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

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.

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

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

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.

Compstatin, a cyclic tridecapeptide, which was originally discovered from phage-display libraries, is a highly potent and selective C3 inhibitor.

Iptacopan hydrochloride (LNP023 hydrochloride) is an orally bioavailable, highly potent and highly selective factor B inhibitor with an IC50 of 10 nM. Iptacopan hydrochloride shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM.

Compstatin TFA, a potent inhibitor of the complement system C3 characterized by species specificity, is a 13-residue cyclic peptide. It selectively binds to baboon C3 and demonstrates resistance to proteolytic cleavage in baboon blood (similar to humans), effectively inhibiting the activation of the primate complement system. Notably, Compstatin TFA exhibits IC 50 values of 63 μM and 12 μM for the classical and alternative complement pathways, respectively [1] [2] [3].

Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses[3]. In C3-/- mice alcohol-induced liver steatosis is absent or strongly reduced after chronic or acute alcohol exposure. This suggests that the complement system and its component C3 contribute to the development of alcohol-induced fatty liver and its consequences[4].AMY-101 TFA (Cp40 TFA) is a peptidic inhibitor of the central complement component C3 (KD: 0.5 nM). It shows a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation[5].a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight) was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria) can additionally benefit in terms of improved periodontal condition[6].Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40.Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3[7].

Danicopan (ACH-4471) (ACH-4471) is a selective, orally active small molecule factor D inhibitor with high binding affinity to human factor D, with a Kd value of 0.54 nM. Danicopan (ACH-4471) inhibits the activity of the complement replacement pathway (APC) and may block the complement replacement pathway in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

FD-IN-1 is a factor D (FD) inhibitor with an IC50 of 12 nM.FD-IN-1 also inhibits factor XIa (FXIa) and Tryptase β2 with IC50s of 7.7 and 6.5μM, respectively. Complement FD, a highly specific S1 serine protease, plays a central role in the alternative complement pathway of the innate immune system.

JR14a (5-(Bis(4-chlorophenyl)methyl)-3-methylthiophene-2-carbonyl)-l-arginine hydrochloride) is a potent antagonist of human complement C3a receptor.

Isatuximab is a monoclonal antibody targeting the transmembrane receptor and extracellular enzyme CD38 in malignant cells of the hematological system and is a highly expressed protein in multiple myeloma. Isatuximab has antitumor activity, antibody-dependent cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cytophagocytosis, which can directly induce apoptosis in the absence of crosslinking. Isatuximab has an inhibitory effect on CD38 extracellular enzyme activity, which is associated with many cellular functions.

(Z)-Leukadherin-1 (ADH-503 free base) is an allosteric agonist of CD11b.

SB290157 trifluoroacetate is a potent and selective antagonist of C3a receptor(IC50 of 200 nM).

Leukadherin-1 is an allosteric activator of CD11b/CD18. Increasing CD11b/CD18-dependent cell adhesion to fibrinogen, Decreasing leukocyte motility and transendothelial migration; reduces inflammation.

Mirococept (APT070), an antibody designed to target the complement system components C3b/C4b and act as a membrane-localizing C3 convertase inhibitor, effectively diminishes the release of C-peptide and pro-inflammatory cytokines. It also curtails the infiltration of inflammatory cells and intraislet inflammation, offering advantages for islet transplantation. Furthermore, Mirococept mitigates increased vascular permeability in intestinal and pulmonary contexts, thereby reducing neutrophil influx [1] [2].

N-((Allyloxy)carbonyl)-N-methyl-L-alanine, an alanine derivative, serves as a precursor for the synthesis of complement factor D inhibitors, which are key in researching immune system-related diseases [1].

Lipoteichoic acid, a polymer of Staphylococcus aureus cell wall, activates the complement system by inducing C3 and inhibiting CD55, and reduces fat deposition via the IGF-1 pathway.

Eculizumab is a recombinant humanized monoclonal antibody against the complement protein C5

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