Page last updated: 2024-11-13

compstatin

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

compstatin: binds to complement 3; amino acid sequence in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID25082538
CHEMBL ID266963
MeSH IDM0289417

Synonyms (13)

Synonym
bdbm50241352
icvvqdwghhrct-nh2
CHEMBL266963 ,
compstatin
S8522
206645-99-0
AC-33698
AKOS024457182
gtpl9218
cid 16220219
Q27076880
CCG-270690
D80482

Research Excerpts

Overview

Compstatin is a 13-residue disulfide-bridged peptide that inhibits a key step in the activation of the human complement system. It was originally identified through phage-mediated presentation of a peptide library to C3b.

ExcerptReferenceRelevance
"Compstatin is a 13-residue cyclic peptide inhibitor of complement activation that was originally identified through phage-mediated presentation of a peptide library to C3b. "( A simple, yet highly accurate, QSAR model captures the complement inhibitory activity of compstatin.
Kaznessis, Y; Lambris, JD; Mulakala, C, 2007
)
2
"Compstatin is a 13-residue peptide that inhibits activation of the complement system by binding to the central component C3 and its fragments C3b and C3c. "( Structure-kinetic relationship analysis of the therapeutic complement inhibitor compstatin.
Kaznessis, YN; Lambris, JD; Magotti, P; Qu, H; Ricklin, D; Wu, YQ,
)
1.8
"Compstatin is a 13-residue disulfide-bridged peptide that inhibits a key step in the activation of the human complement system. "( Novel analogues of the therapeutic complement inhibitor compstatin with significantly improved affinity and potency.
Kaznessis, YN; Kourtzelis, I; Lambris, JD; Magotti, P; Qu, H; Ricklin, D; Wu, EL; Wu, YQ, 2011
)
2.06
"Compstatin is a 13-residue cyclized peptide that inhibits cleavage of complement protein C3, preventing downstream complement activation."( A new generation of potent complement inhibitors of the Compstatin family.
Bellows-Peterson, ML; Floudas, CA; Gorham, RD; Ling, J; Lo, DD; López de Victoria, A; Morikis, D, 2011
)
1.34
"Compstatin is a 13-residue cyclic peptide that has the potential to become a therapeutic agent against unregulated complement activation. "( Conformational interconversion in compstatin probed with molecular dynamics simulations.
Lambris, JD; Mallik, B; Morikis, D, 2003
)
2.04
"Compstatin is a 13-residue cyclic peptide that has the ability to inhibit the cleavage of C3 to C3a and C3b. "( Improvement of the anti-C3 activity of compstatin using rational and combinatorial approaches.
Floudas, CA; Klepeis, JL; Lambris, JD; Mallik, B; Morikis, D; Soulika, AM, 2004
)
2.04
"Compstatin is a 13-residue cyclic peptide that inhibits complement activation by binding to complement component, C3. "( Thermodynamic studies on the interaction of the third complement component and its inhibitor, compstatin.
Katragadda, M; Lambris, JD; Morikis, D, 2004
)
1.99
"Compstatin is a peptidic complement inhibitor that prevents the cleavage of complement factor 3 (C3) by C3 convertase. "( Compstatin inhibits complement activation by binding to the beta-chain of complement factor 3.
Holland, MC; Lambris, JD; Sahu, A; Sfyroera, G; Soulika, AM, 2006
)
3.22

Treatment

ExcerptReferenceRelevance
"Compstatin treatment also improved cardiac function and the biochemical markers of kidney and liver damage."( Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis.
Ivanciu, L; Kinasewitz, G; Lambris, JD; Lupu, C; Lupu, F; Magotti, P; Mollnes, TE; Peer, G; Popescu, NI; Sfyroera, G; Silasi-Mansat, R; Taylor, FB; Zhu, H, 2010
)
1.08

Pharmacokinetics

ExcerptReferenceRelevance
" Here, we report improvements in both the inhibitory potency and pharmacokinetic parameters of compstatin that broaden its clinical applications."( New analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties.
Bai, H; Barlow, PN; Chen, H; DeAngelis, RA; Lambris, JD; Lupu, F; Maciejewski, M; Qu, H; Reis, ES; Resuello, RR; Ricklin, D; Tzekou, A, 2013
)
0.86
" Although recent analogues show beneficial pharmacokinetics, further extension of the plasma half-life is expected to benefit systemic application of these peptidic inhibitors."( Conjugation to albumin-binding molecule tags as a strategy to improve both efficacy and pharmacokinetic properties of the complement inhibitor compstatin.
Huang, Y; Knerr, PJ; Lambris, JD; Reis, ES; Ricklin, D; van der Donk, WA, 2014
)
0.6
" Three of the new derivatives showed improved pharmacokinetic profiles in vivo in non-human primates."( New Analogs of the Complement C3 Inhibitor Compstatin with Increased Solubility and Improved Pharmacokinetic Profile.
Alayi, TD; Berger, N; Lambris, JD; Reis, ES; Resuello, RRG; Tuplano, JV, 2018
)
0.74

Bioavailability

ExcerptReferenceRelevance
" For example, 6e is an orally active inhibitor of human neutrophil elastase that entered human clinical studies, 52h is an orally bioavailable inhibitor of human chymase, and 82m is a FAAH inhibitor with in vivo endocannabinoid-enhancing activity."( Inhibitors of proteases and amide hydrolases that employ an alpha-ketoheterocycle as a key enabling functionality.
Costanzo, MJ; Maryanoff, BE, 2008
)
0.35

Dosage Studied

ExcerptRelevanceReference
" Dose-response curves for each inhibitor were generated."( In vitro Inhibition of Canine Complement-Mediated Hemolysis.
Behling-Kelly, E; Goggs, R; Hernandez, DM, 2018
)
0.48
" The development of cost-effective treatment options with suitable dosing route and schedule will be critical for patients with complement mediated chronic diseases."( Evolution of compstatin family as therapeutic complement inhibitors.
Huang, Y, 2018
)
0.85
" Given their compelling solubility and pharmacokinetic profiles, these new Cp40 analogs should broaden the spectrum of administration routes, likely reducing dosing frequency during chronic treatment and potentially expanding their range of clinical application."( New Analogs of the Complement C3 Inhibitor Compstatin with Increased Solubility and Improved Pharmacokinetic Profile.
Alayi, TD; Berger, N; Lambris, JD; Reis, ES; Resuello, RRG; Tuplano, JV, 2018
)
0.74
" Cynomolgus monkeys were dosed subcutaneously with Cp40, resulting in systemic inhibition of C3, for 1 week, 2 weeks, or 3 months."( Safety profile after prolonged C3 inhibition.
Berger, N; Biglarnia, AR; Doot, RK; Foukas, PG; Gumas, JT; Hajishengallis, G; Huber-Lang, M; Kajikawa, T; Koutsogiannaki, S; Kukis, D; Lambris, JD; Mastellos, DC; Nilsson, B; Reis, ES; Resuello, RRG; Soulika, AM; Tarantal, AF; Tuplano, JV; Wang, X; Yancopoulou, D; Young, AJ, 2018
)
0.48
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Complement factor BHomo sapiens (human)IC50 (µMol)7.70003.40003.40003.4000AID321220; AID475586
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (29)

Processvia Protein(s)Taxonomy
proteolysisComplement factor BHomo sapiens (human)
complement activation, alternative pathwayComplement factor BHomo sapiens (human)
complement activationComplement factor BHomo sapiens (human)
response to bacteriumComplement factor BHomo sapiens (human)
positive regulation of type IIa hypersensitivityComplement C3Homo sapiens (human)
positive regulation of protein phosphorylationComplement C3Homo sapiens (human)
positive regulation of activation of membrane attack complexComplement C3Homo sapiens (human)
complement receptor mediated signaling pathwayComplement C3Homo sapiens (human)
fatty acid metabolic processComplement C3Homo sapiens (human)
inflammatory responseComplement C3Homo sapiens (human)
immune responseComplement C3Homo sapiens (human)
complement activationComplement C3Homo sapiens (human)
complement activation, alternative pathwayComplement C3Homo sapiens (human)
complement activation, classical pathwayComplement C3Homo sapiens (human)
signal transductionComplement C3Homo sapiens (human)
G protein-coupled receptor signaling pathwayComplement C3Homo sapiens (human)
response to bacteriumComplement C3Homo sapiens (human)
positive regulation of vascular endothelial growth factor productionComplement C3Homo sapiens (human)
positive regulation of glucose transmembrane transportComplement C3Homo sapiens (human)
regulation of triglyceride biosynthetic processComplement C3Homo sapiens (human)
positive regulation of lipid storageComplement C3Homo sapiens (human)
neuron remodelingComplement C3Homo sapiens (human)
oviduct epithelium developmentComplement C3Homo sapiens (human)
positive regulation of G protein-coupled receptor signaling pathwayComplement C3Homo sapiens (human)
positive regulation of angiogenesisComplement C3Homo sapiens (human)
positive regulation of receptor-mediated endocytosisComplement C3Homo sapiens (human)
positive regulation of phagocytosis, engulfmentComplement C3Homo sapiens (human)
amyloid-beta clearanceComplement C3Homo sapiens (human)
complement-dependent cytotoxicityComplement C3Homo sapiens (human)
complement-mediated synapse pruningComplement C3Homo sapiens (human)
vertebrate eye-specific patterningComplement C3Homo sapiens (human)
positive regulation of apoptotic cell clearanceComplement C3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (6)

Processvia Protein(s)Taxonomy
complement bindingComplement factor BHomo sapiens (human)
serine-type endopeptidase activityComplement factor BHomo sapiens (human)
protein bindingComplement factor BHomo sapiens (human)
endopeptidase inhibitor activityComplement C3Homo sapiens (human)
signaling receptor bindingComplement C3Homo sapiens (human)
protein bindingComplement C3Homo sapiens (human)
C5L2 anaphylatoxin chemotactic receptor bindingComplement C3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (10)

Processvia Protein(s)Taxonomy
extracellular regionComplement factor BHomo sapiens (human)
extracellular spaceComplement factor BHomo sapiens (human)
plasma membraneComplement factor BHomo sapiens (human)
extracellular exosomeComplement factor BHomo sapiens (human)
blood microparticleComplement factor BHomo sapiens (human)
extracellular regionComplement C3Homo sapiens (human)
extracellular spaceComplement C3Homo sapiens (human)
endoplasmic reticulum lumenComplement C3Homo sapiens (human)
plasma membraneComplement C3Homo sapiens (human)
cell surfaceComplement C3Homo sapiens (human)
secretory granule lumenComplement C3Homo sapiens (human)
azurophil granule lumenComplement C3Homo sapiens (human)
extracellular exosomeComplement C3Homo sapiens (human)
blood microparticleComplement C3Homo sapiens (human)
protein-containing complexComplement C3Homo sapiens (human)
extracellular spaceComplement C3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (13)

Assay IDTitleYearJournalArticle
AID1393239Inhibition of C3 (unknown origin)-binding to convertase of classical pathway by hemolytic assay2018Journal of medicinal chemistry, 04-26, Volume: 61, Issue:8
Chemical Approaches to Modulating Complement-Mediated Diseases.
AID475586Inhibition of human C3/C5 convertase assessed as inhibition of C3 cleavage2009Journal of medicinal chemistry, Oct-08, Volume: 52, Issue:19
Structure-activity relationships for substrate-based inhibitors of human complement factor B.
AID1195926Solubility of the compound in PBS at pH 7.4 after 24 to 48 hrs by spectrophotometry2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
New compstatin peptides containing N-terminal extensions and non-natural amino acids exhibit potent complement inhibition and improved solubility characteristics.
AID1195923Inhibition of complement activation in human fetal RPE cells assessed as hemolysis of serum-treated rabbit erythrocytes compound preincubated with serum for 15 mins measured 20 mins after erythrocyte addition by hemolytic assay2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
New compstatin peptides containing N-terminal extensions and non-natural amino acids exhibit potent complement inhibition and improved solubility characteristics.
AID1195921Inhibition of C3 cleavage in human serum assessed as reduction in C3b formation compound preincubated for 15 mins measured 1 hr post LPS stimulation by ELISA2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
New compstatin peptides containing N-terminal extensions and non-natural amino acids exhibit potent complement inhibition and improved solubility characteristics.
AID385500Inhibition of complement component C3c2007The Journal of biological chemistry, Oct-05, Volume: 282, Issue:40
Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition.
AID385502Binding affinity to complement component C3c in human plasma2007The Journal of biological chemistry, Oct-05, Volume: 282, Issue:40
Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition.
AID310881Inhibition of C3b activation relative to compstatin2007Bioorganic & medicinal chemistry, Feb-15, Volume: 15, Issue:4
A simple, yet highly accurate, QSAR model captures the complement inhibitory activity of compstatin.
AID321220Inhibition of C3 convertase2008Bioorganic & medicinal chemistry, Feb-15, Volume: 16, Issue:4
Inhibitors of proteases and amide hydrolases that employ an alpha-ketoheterocycle as a key enabling functionality.
AID1195922Inhibition of C3 cleavage in human serum assessed as reduction in C5b-9 formation compound preincubated for 15 mins measured 1 hr post LPS stimulation by ELISA2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
New compstatin peptides containing N-terminal extensions and non-natural amino acids exhibit potent complement inhibition and improved solubility characteristics.
AID1195925Inhibition of complement activation in human fetal RPE cells assessed as reduction in C5b-9 formation at 50 uM by fluorescence assay in presence of complement-competant human serum2015Journal of medicinal chemistry, Jan-22, Volume: 58, Issue:2
New compstatin peptides containing N-terminal extensions and non-natural amino acids exhibit potent complement inhibition and improved solubility characteristics.
AID385501Binding affinity to complement component C3 in human plasma by isothermal titration calorimetry2007The Journal of biological chemistry, Oct-05, Volume: 282, Issue:40
Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition.
AID1393237Inhibition of C3 (unknown origin)-binding to convertase of alternative pathway by hemolytic assay2018Journal of medicinal chemistry, 04-26, Volume: 61, Issue:8
Chemical Approaches to Modulating Complement-Mediated Diseases.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (97)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's3 (3.09)18.2507
2000's33 (34.02)29.6817
2010's47 (48.45)24.3611
2020's14 (14.43)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 31.60

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index31.60 (24.57)
Research Supply Index4.62 (2.92)
Research Growth Index5.18 (4.65)
Search Engine Demand Index42.09 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (31.60)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (1.00%)5.53%
Reviews15 (15.00%)6.00%
Case Studies1 (1.00%)4.05%
Observational0 (0.00%)0.25%
Other83 (83.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]