| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
Compstatin is a novel and potent 13-residue cyclic peptide acting as a potent inhibitor of the complement system C3 with species specificity. Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans). Compstatin specifically inhibits complement activation in primates. Its inhibitory potency, measured as IC50, differs between the two complement pathways: it exhibits an IC50 of 63 μM for the classical pathway and 12 μM for the alternative pathway.
| Targets |
- The target is complement component C3 (the specific binding region is macroglobulin (MG) domains 4 and 5 of C3c). It can block C3 convertase-mediated C3 cleavage to inhibit complement activation; it only has inhibitory activity on the primate complement system[3]
- It can bind to C3, C3b and C3c, but not to C3d, and the binding site is located in the C3c region of C3[4] |
|---|---|
| ln Vitro |
Comprestatin in human blood has an in vitro half-life of roughly two hours [2]. Comprestatin creates pearl clusters in solution when it rotates β on the Gln-5-Gly-8 residue with the disulfide bridge Cys-2-Cys12, residues Ile-1-Val-4 and Thr-13 [3].
- In the model of pig kidney perfused ex vivo with fresh human blood, the median survival time of pig xenografts in the Compstatin-treated group was 380 min, which was significantly longer than 90 min in the control group (P=0.0036); within the first 60 min, the classical complement pathway (C1rs-C1inhibitor, C4bc) was significantly activated in both groups with similar activation levels, but the C3 activation products increased 5-fold and the terminal complement complex increased 8-fold in the control group, while no such increase was observed in the Compstatin group; immunohistochemistry showed less C3 and fibrin deposition in the Compstatin group, and immunoelectron microscopy showed less deposition of terminal complement complex SC5b-9; significant changes were observed in total white blood cell count, neutrophil count, myeloperoxidase level and expression of surface activation markers CD11b, CD35 and CD62L in both groups, and the degree of leukocyte activation in the Compstatin group was lower but without statistical significance; there were no differences in platelet count, thrombospondin, soluble P-selectin and β-thromboglobulin levels between the two groups[2] - The synthetic 27-amino acid parent peptide can bind to C3 and its cleavage fragments, and has inhibitory effects on both the classical and alternative complement pathways, with reversible inhibition; its activity is concentrated in the N-terminal 13-amino acid cyclic peptide region (ICVVQDWGHHRCT), and reductive alkylation of this cyclic peptide will completely lose its complement inhibitory activity; the peptide can inhibit C3 cleavage in normal human serum and in the reconstituted alternative pathway system, without affecting factor B cleavage or properdin binding to C3[4] |
| ln Vivo |
When compstatin (21 mg/kg) was administered as a combination bolus and infusion medication, total suppression was seen. Compstatin fully prevents heart rate, systemic, central, and pulmonary arterial pressure from being negatively impacted by heparin/protamine-induced complement activation in vivo [1]. In baboons smoking, paroxetine remains constant for almost twenty-four hours [1]. Pig xenografts in the comprestatin-infused group had a substantially longer transitory period than those in the saline group [2].
- In the baboon in vivo model, Compstatin was administered via a combination of bolus injection and infusion, and when the total dose reached 21 mg/kg, it could completely inhibit heparin/protamine complex-induced complement activation; it had no adverse effects on baboons' heart rate, systemic arterial pressure, central venous pressure and pulmonary arterial pressure[1] |
| Enzyme Assay |
- Phage-displayed random peptide libraries were screened for peptides that can bind to C3b, and then corresponding peptides and overlapping peptides were synthesized to verify their binding ability to C3 and its cleavage fragments; meanwhile, the effects of the peptides on the interactions of key components in the complement pathway (such as factor B and properdin) were detected to clarify their inhibitory effect on C3 cleavage[4]
- The crystal structure of the Compstatin-C3c complex was resolved by crystallographic techniques to clarify the binding site and molecular conformational changes after binding, and then the molecular mechanism of complement activation inhibition was deduced[3] |
| 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.
|
| Animal Protocol |
Animal/Disease Models: Juvenile baboons (P. Anubis) weigh 10.5-28.8 kg [1].
Doses: 50, 25 mg/kg, 60 minutes after heparin injection, 2 minutes before protamine injection. Route of Administration: Push Note. Experimental Results: Complete inhibition of complement activation induced by heparin-protamine complex. - Baboon in vivo complement activation inhibition experiment: Baboons were selected as experimental animals (because Compstatin can bind to baboon C3 and is resistant to proteolytic cleavage in baboon blood, similar to that in humans); Compstatin was administered via a combination of bolus injection and infusion with a total dose of 21 mg/kg; after administration, a heparin/protamine complex-induced complement activation model was established, and the complement activation level and physiological indicators such as heart rate and blood pressure at various sites were monitored[1] - Pig xenograft ex vivo perfusion experiment: Pig kidneys were used to construct an ex vivo perfusion model, and the perfusate was fresh human blood containing Compstatin (n=6) or control reagent (n=6); the survival time of the transplanted kidney, the activation state of complement, leukocytes and platelets in the body fluid were continuously monitored, and the deposition of complement-related components in the tissue was detected by immunohistochemistry and immunoelectron microscopy[2] |
| ADME/Pharmacokinetics |
Compstatin has anti-protein hydrolysis properties in baboon blood, which are similar to its metabolic properties in humans [1] - Compstatin has the potential to be developed into oral formulations [1]
|
| Toxicity/Toxicokinetics |
At a dose of 21 mg/kg, Compstatin had no adverse effects on physiological parameters such as heart rate, systemic arterial pressure, central venous pressure, and pulmonary artery pressure in baboons, and no obvious toxicity was observed [1]
|
| References |
|
| Additional Infomation |
Compstatin is a cyclic peptide complement inhibitor composed of 13 amino acids. Its mechanism of inhibiting complement activation is by binding to C3, which spatially blocks the binding of substrate C3 to the invertase complex, thereby blocking complement activation and amplification[3]. Compstatin activation products are major components of inflammatory responses induced by cardiac surgery and cardiopulmonary bypass, which can lead to postoperative organ dysfunction, fluid retention, and increased morbidity. Compstatin has the potential to prevent complement activation during and after clinical cardiac surgery[1]. Compstatin may be used to alleviate hyperacute rejection in xenotransplantation by inhibiting C3 and blocking activation of the terminal complement pathway[2].
|
| Molecular Formula |
C66H99N23O17S2
|
|---|---|
| Molecular Weight |
1550.7662
|
| Exact Mass |
1549.7
|
| CAS # |
206645-99-0
|
| Related CAS # |
Compstatin TFA
|
| PubChem CID |
25082538
|
| Appearance |
White to off-white solid powder
|
| LogP |
1.402
|
| Hydrogen Bond Donor Count |
22
|
| Hydrogen Bond Acceptor Count |
23
|
| Rotatable Bond Count |
25
|
| Heavy Atom Count |
108
|
| Complexity |
3180
|
| Defined Atom Stereocenter Count |
14
|
| SMILES |
C([C@H]1C(NCC(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](CSSC[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N1)=O)CC(=O)O)=O)CCC(=O)N)=O)C(C)C)=O)C(C)C)=O)NC(=O)[C@@H](N)[C@@H](C)CC)C(=O)N[C@H](C(=O)N)[C@H](O)C)=O)CCCNC(N)=N)=O)CC1NC=NC=1)=O)CC1NC=NC=1)=O)=O)C1=CNC2=CC=CC=C12
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
H2O : ~100 mg/mL (~64.48 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (64.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6448 mL | 3.2242 mL | 6.4484 mL | |
| 5 mM | 0.1290 mL | 0.6448 mL | 1.2897 mL | |
| 10 mM | 0.0645 mL | 0.3224 mL | 0.6448 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
