Complement System Inhibitor

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].

Sefaxersen sodium is a specific antisense oligonucleotide (ASO) targeting complement factor B (CFB). Sefaxersen sodium effectively reduces circulating levels of CFB, and can be used for geographic atrophy (GA) research.

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

Cemdisiran (ALN-CC5) is an N-acetylgalactosamine-conjugated RNAi agent and also a complement component C5 inhibitor. Cemdisiran targets C5 mRNA, cleaves C5 mRNA via the endogenous RNA interference pathway, and inhibits the production of C5 protein in the liver. Cemdisiran exerts a dose-dependent inhibitory effect on total C5 concentrations in cynomolgus monkeys. When used in combination with Pozelimab (HY-P99786) in cynomolgus monkeys, Cemdisiran achieves a more sustained and complete inhibitory effect on complement activity. Cemdisiran can be used in the research of paroxysmal nocturnal hemoglobinuria and other complement-mediated diseases.

Pozelimab (REGN3918) is a fully human IgG4 anti-C5 monoclonal antibody. Pozelimab binds to C5 and C5 variants with high affinity and blocks complement-mediated hemolysis. Pozelimab can be used for the research of complement-mediated diseases.

C1s-IN-1 trihydrochloride (Compound A1) is the selective inhibitor for C1s protease with the K_i of 5.8 μM. C1s-IN-1 trihydrochloride inhibits cleavage of C2 by C1s with an IC₅₀ of 85 μM, inhibits the activation of classic pathway with an IC₅₀ of 22 μM. C1s-IN-1 trihydrochloride is the competitive inhibitor for thrombin with the K_i of 51.2 μM.

Dexamethasone-4,6α,21,21-d₄ is the deuterium labeled Dexamethasone-4,6α,21,21. Dexamethasone (Hexadecadrol) is a glucocorticoid receptor agonist. Dexamethasone also significantly decreases CD11b, CD18, and CD62L expression on neutrophils, and CD11b and CD18 expression on monocytes. Dexamethasone is highly effective in the control of COVID-19 infection. Dexamethasone inhibits production of exosomes containing inflammatory microRNA-155 in lipopolysaccharide-induced macrophage inflammatory responses.

Pelecopan (BCX9930) is a potent, selective, orally active inhibitor of complement factor D with an IC₅₀ value of 14.3 nM. Pelecopan can target factor D to prevent both intravascular and extravascular hemolysis in PNH. Pelecopan also be used for other alternative pathway (AP) mediated diseases.

Factor D inhibitor 6 is a potent, highly selective and orally active factor D (FD) inhibitor with an IC₅₀ of 30 nM and a K_d of 6 nM. Factor D inhibitor 6 is inactive against factor B, lassical and lectin complement-pathway activation, and a broad assay panel of receptors, ion channels, kinases and proteases.

tLyP-1 peptide is an NRP-1 targeting peptide with an IC₅₀ of 4 μM, and its amino acid sequence is CGNKRTR. tLyP-1 peptide specifically binds to NRP-1 to target tumor cells.

PIC1 PA TFA is the trifluoroacetate salt form of PIC1 PA (HY-P10827). PIC1 PA TFA is a 15-amino acid peptide that is a potent PIC1 analog that inhibits classical complement activation.

Aristolone is a sesquiterpene that can be isolated from Aristolochia debilis, Rosmarinus officinalis and Ficus Auriculata. Aristolone in Ara Fruit can be used as a prediction of apoptosis in HeLa cells. Aristolone inhibits the C1 complement component. Aristolone produces cytotoxicity effects on cells. Aristolone has anticancer properties and can be studied in research for cervical cancer.

Cemdisiran sodium (ALN-CC5 sodium) is an N-acetylgalactosamine-conjugated RNAi agent and also a complement component C5 inhibitor. Cemdisiran sodium targets C5 mRNA, cleaves C5 mRNA via the endogenous RNA interference pathway, and inhibits the production of C5 protein in the liver. Cemdisiran sodium exerts a dose-dependent inhibitory effect on total C5 concentrations in cynomolgus monkeys. When used in combination with Pozelimab (HY-P99786) in cynomolgus monkeys, Cemdisiran sodium achieves a more sustained and complete inhibitory effect on complement activity. Cemdisiran sodium can be used in the research of paroxysmal nocturnal hemoglobinuria and other complement-mediated diseases.

3-Phenoxybenzaldehyde has weak complement classical pathway inhibition and hemolytic activity.

PIC1 PA, a 15 amino-acid peptide, is a potent PIC1 analog that inhibits classical pathway mediated complement activation. PIC1 PA functionally disrupts the C1s-C1r-C1r-C1s/MASPs interaction with collagen-like region (CLR) of C1q/MBL, respectively. PIC1 PA specifically binds to the CLR of C1q and bounds to purified C1q with a mean equilibrium dissociation constant (KD) of 33.3 nM.

Compstatin TFA, a 13-residue cyclic peptide, is a potent inhibitor of the complement system C3 with species specificity. Compstatin TFA binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans). Compstatin TFA inhibits only the activation of primates’ complement system. Compstatin TFA exhibits IC₅₀ values of 63 μM and 12 μM for classical and alterative complement pathway, respectively.

Ruxoprubart (NM8074) is an inhibitor of complement factor B (Bb subunit). Ruxoprubart selectively binds to active Bb to inhibit the alternative complement pathway without affecting the classical complement pathway. By blocking the activities of AP C3 and C5 convertases, Ruxoprubart effectively inhibits red blood cell hemolysis and reduces C3b deposition, thereby preventing intravascular and extravascular hemolysis. Ruxoprubart can be used in research related to paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, C3 glomerulopathy, and IgA nephropathy.

Complement C1s-IN-1 is a potent, selective, orally active and cross the blood-brain barrier C1s inhibitor with an IC₅₀ value of 36 nM.