| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Human complement component C3 (specifically the β-chain)
Compstatin binds to and inhibits complement component C3. It shows species specificity, being active against primate C3 (including human and baboon) but not against non-primate C3. Binding affinity studies using surface plasmon resonance indicate it binds to native C3, C3b, and C3c, but not to C3d. The affinity for C3b and C3c is reported to be 22-fold and 74-fold lower, respectively, than for native C3 . |
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| ln Vitro |
In vitro, compstatin has a half-life of roughly two hours in human blood[2]. Compstatin creates a hydrophobic cluster in solution by producing a β-turn at residues Gln-5–Gly-8, Ile–1–Val–4, and Thr–13, along with the disulfide bridge Cys-2–Cys12[3].
Compstatin inhibits complement activation in human serum. In an ex vivo pig kidney xenograft model perfused with fresh human blood, Compstatin (administered at a concentration in the blood of 60 µM) completely inhibited the generation of C3 activation products and terminal complement complex (TCC/C5b-9) over a 60-minute observation period, whereas in the control group these products increased fivefold and eightfold, respectively . Structural studies using 2D NMR determined that Compstatin contains a type I β-turn (Gln5-Asp6-Trp7-Gly8), which is critical for its conformational stability and functional activity . Alanine scanning mutagenesis studies revealed that residues Val3, Gln5, Asp6, Trp7, and Gly8 are crucial for inhibitory activity, with substitution of Gly8 causing a 100-fold decrease in potency. In contrast, substitution of Val4, His9, His10, and Arg11 resulted in minimal change in activity . |
| ln Vivo |
When administered as a bolus injection plus infusion, compstatin (21 mg/kg) results in total suppression. Compstatin completely prevents complement activation generated by heparin and prostamine in vivo, however without changing heart rate or pulmonary, central venous, or systemic artery pressures [1]. In baboon plasma, compstatin is stable for more than 24 hours[1]. The group that received Compstatin perfusion had a considerably longer survival rate for pig xenografts than the control group [2].
In a baboon model of heparin/protamine complex-induced complement activation (a simulation of cardiac surgery inflammation), intravenous Compstatin (total dose of 21 mg/kg administered as a combination of bolus and infusion) completely inhibited in vivo complement activation. This inhibition occurred without adversely affecting heart rate, systemic arterial pressure, central venous pressure, or pulmonary arterial pressure, indicating a favorable safety profile in this acute setting . |
| Enzyme Assay |
The binding kinetics of Compstatin to C3 and its fragments were analyzed using surface plasmon resonance (SPR). Purified human complement proteins (native C3, C3b, C3c) were immobilized on a sensor chip. Compstatin in solution was flowed over the chip at various concentrations to measure association and dissociation rates. The data showed that binding to native C3 was biphasic, while binding to C3b and C3c followed a 1:1 Langmuir binding model, allowing for the calculation of comparative binding affinities .
A photo-crosslinking study was performed to identify the binding site on C3. A Compstatin analog containing a photoactivatable amino acid (Bpa) was synthesized. This analog was incubated with purified C3 protein and then exposed to UV light to form a covalent bond between the peptide and its binding site on C3. Subsequent analysis (SDS-PAGE, immunoblotting) identified a 40-kDa region on the β-chain of C3 as the binding site . |
| Cell Assay |
Not explicitly detailed in the provided search results for the specified articles. However, related work (referenced in ) mentions the use of hemolysis assays (complement-mediated lysis of red blood cells) to evaluate the inhibitory activity of Compstatin and its analogs, confirming its function in preventing membrane attack complex formation.
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| Animal Protocol |
Animal/Disease Models: Juvenile baboons (P. Anubis) weighing 10.5-28.8 kg[1].
Doses: 50, 25 mg/kg 60 min after heparin and 2 min before protamine. Route of Administration: A bolus injection. Experimental Results: Completely inhibited complement activation induced by heparin–protamine complexes. Baboon Model of Heparin/Protamine-Induced Inflammation: Adult baboons were anesthetized and instrumented for hemodynamic monitoring. Compstatin was administered intravenously. The dosing regimen that achieved complete inhibition consisted of an initial intravenous bolus, followed by a continuous infusion, totaling 21 mg/kg. Heparin and protamine were subsequently administered to induce complement activation, and blood samples were taken to measure complement activation products . Ex Vivo Pig Xenograft Perfusion Model: Kidneys from Norwegian Landrace pigs were surgically removed. An ex vivo perfusion circuit was established using fresh, heparinized human AB blood from healthy volunteers. Compstatin was directly added to the human blood reservoir at a final concentration of 60 µM before the start of kidney perfusion. Perfusion conditions (temperature, oxygenation, pH) were carefully controlled to mimic physiological conditions. Graft survival was defined as the time until a sharp rise in vascular resistance rendered perfusion impossible . |
| ADME/Pharmacokinetics |
An in vitro human blood biotransformation study showed that the main degradation pathway of Compstatin is the enzymatic removal (cleavage) of the N-terminal isoleucine (Ile1) residue. This degradation can be blocked by chemically modifying the peptide through N-acetylation, resulting in a more stable analog that is less susceptible to enzymatic degradation in the blood.
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| Toxicity/Toxicokinetics |
In the baboon study, an effective anticomplement dose of Compstatin (21 mg/kg, intravenously) did not cause any adverse hemodynamic effects, such as changes in heart rate or blood pressure, indicating that there was no acute cardiovascular toxicity at this dose in the study model.
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| References |
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| Additional Infomation |
Compstatin is a 13-amino acid cyclic peptide discovered by screening a phage-displayed library of random peptides antagonistic to C3b. Its sequence is Ile-Cys-Val-Val-Gln-Asp-Trp-Gly-His-His-Arg-Cys-Thr, cyclized via a disulfide bond between Cys2 and Cys12. It inhibits three complement activation pathways (classical, lectin, and alternative pathways) by binding to C3 and preventing proteolytic cleavage by C3 convertases, thereby blocking the generation of downstream effector molecules such as C3a, C5a, and the membrane attack complex (C5b-9). Due to its species-specificity for primate C3, non-human primate models (such as baboons) are crucial for preclinical in vivo evaluation. Compstatin is considered the prototype for designing complement-targeted therapies, and has been used to develop multiple generations of analogues with stronger efficacy and better drug properties for clinical development in various inflammatory diseases.
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| Molecular Formula |
C68H100F3N23O19S2
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|---|---|
| Molecular Weight |
1664.79
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| Exact Mass |
1565.73437
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| Related CAS # |
Compstatin;206645-99-0
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| PubChem CID |
172873810
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
22
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| Hydrogen Bond Acceptor Count |
23
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| Rotatable Bond Count |
25
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| Heavy Atom Count |
109
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| Complexity |
3170
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| Defined Atom Stereocenter Count |
14
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| SMILES |
C.CC[C@H](C)[C@@H](C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC1=O)C(C)C)C(C)C)CCC(=O)N)CC(=O)O)CC2=CNC3=CC=CC=C32)CC4=CN=CN4)CC5=CN=CN5)CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N)N
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| InChi Key |
NNKABSGFRUMXBK-MIGPDYDPSA-N
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| InChi Code |
InChI=1S/C66H99N23O17S2.CH4/c1-8-32(6)50(68)63(104)86-46-27-108-107-26-45(62(103)89-53(33(7)90)54(69)95)85-56(97)39(14-11-17-74-66(70)71)80-59(100)43(20-36-24-73-29-78-36)83-58(99)42(19-35-23-72-28-77-35)79-48(92)25-76-55(96)41(18-34-22-75-38-13-10-9-12-37(34)38)82-60(101)44(21-49(93)94)84-57(98)40(15-16-47(67)91)81-64(105)51(30(2)3)88-65(106)52(31(4)5)87-61(46)102;/h9-10,12-13,22-24,28-33,39-46,50-53,75,90H,8,11,14-21,25-27,68H2,1-7H3,(H2,67,91)(H2,69,95)(H,72,77)(H,73,78)(H,76,96)(H,79,92)(H,80,100)(H,81,105)(H,82,101)(H,83,99)(H,84,98)(H,85,97)(H,86,104)(H,87,102)(H,88,106)(H,89,103)(H,93,94)(H4,70,71,74);1H4/t32-,33+,39-,40-,41-,42-,43-,44-,45-,46-,50-,51-,52-,53-;/m0./s1
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| Chemical Name |
2-[(4R,7S,10S,13S,19S,22S,25S,28S,31S,34R)-4-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-34-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-25-(3-amino-3-oxopropyl)-7-[3-(diaminomethylideneamino)propyl]-10,13-bis(1H-imidazol-5-ylmethyl)-19-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27,30,33-decaoxo-28,31-di(propan-2-yl)-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacont-22-yl]acetic acid;methane
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~60.07 mM)
H2O :~50 mg/mL (~30.03 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (1.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (1.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (1.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6007 mL | 3.0034 mL | 6.0068 mL | |
| 5 mM | 0.1201 mL | 0.6007 mL | 1.2014 mL | |
| 10 mM | 0.0601 mL | 0.3003 mL | 0.6007 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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