258
glomerulonephritis, and allergic and asthmatic complications and protected from
xenograft rejections. Phase I clinical trial with this agent in myocardial infarction
and in severe burn-induced respiratory discomfort were found promising. A mutant
version of sCR1 lacking LHR-A sCR1 was then developed to selectively inhibit
alternative complement pathway. However, selective inhibition of classical pathway
was found more effective in facilitating protection from myocardial ischemic injury.
Many protein inhibitors have been developed in this line and are illustrated in
Table 10.5.
Soluble protein inhibitors possess the disadvantage of inhibiting a range of complement split products as they are not very selective against individual members.
Therefore, anti-C5 and anti-C3 monoclonal antibodies were developed against individual complement components for immunotherapy-mediated complement inhibition to reduce tissue injury (Mollnes and Kirschfink 2006; Perricone et al. 2011;
Petering et al. 2000; Scully et al. 2010). Many synthetic peptides and their analogs
have been developed against the most active components in the complement system
such as C5a, C3a, and C3b and to their receptors (Ehrnthaller et al. 2011; Perricone
et al. 2011; Petering et al. 2000; Scully et al. 2010). L156602 is a cyclic peptide
isolated from Streptomyces against C5aR. But the clinical trial has been called off
Table 10.5 Synthetic complement inhibitors
Inhibitor types
Chemical structure
Site of action
Peptide analogs and
derivatives
C5a
C5aR antagonist
C5a, C-terminal octapeptides
C5aR antagonist
C5a, His
67 modified C terminal
octapeptide analogs
C5aR antagonist
C5aR antagonist
C5a
C5aR antagonist
C5a hexapeptide
C5aR antagonist
Peptide with aromatic
substistutions (C089)
C5aR
C5aR antagonist
C3a terminus
C3aR antagonist
PR226 peptide
C3b based phage display screening C3
CH2 domain of human IgG
C1q
C3 convertase
Factor B related hexapeptides
Factor D
C1q B chain helical region
C1q
C3
C3
CBP2 peptide
K76
Factor D
K76
Factor D
K76 analogs and derivatives
K76
Factor D
BCX-1470 (analog)
Nafamstat mesilate
Classical and alternate
pathway
TKIXc (derivative)
Oligodeoxy ribonucleotide
Classical and alternate
pathway
K 76 COOH
FUT-175
PS-oligo
B.C. Bhavya and M. Haridas
glomerulonephritis, and allergic and asthmatic complications and protected from
xenograft rejections. Phase I clinical trial with this agent in myocardial infarction
and in severe burn-induced respiratory discomfort were found promising. A mutant
version of sCR1 lacking LHR-A sCR1 was then developed to selectively inhibit
alternative complement pathway. However, selective inhibition of classical pathway
was found more effective in facilitating protection from myocardial ischemic injury.
Many protein inhibitors have been developed in this line and are illustrated in
Table 10.5.
Soluble protein inhibitors possess the disadvantage of inhibiting a range of complement split products as they are not very selective against individual members.
Therefore, anti-C5 and anti-C3 monoclonal antibodies were developed against individual complement components for immunotherapy-mediated complement inhibition to reduce tissue injury (Mollnes and Kirschfink 2006; Perricone et al. 2011;
Petering et al. 2000; Scully et al. 2010). Many synthetic peptides and their analogs
have been developed against the most active components in the complement system
such as C5a, C3a, and C3b and to their receptors (Ehrnthaller et al. 2011; Perricone
et al. 2011; Petering et al. 2000; Scully et al. 2010). L156602 is a cyclic peptide
isolated from Streptomyces against C5aR. But the clinical trial has been called off
Table 10.5 Synthetic complement inhibitors
Inhibitor types
Chemical structure
Site of action
Peptide analogs and
derivatives
C5a
C5aR antagonist
C5a, C-terminal octapeptides
C5aR antagonist
C5a, His
67 modified C terminal
octapeptide analogs
C5aR antagonist
C5aR antagonist
C5a
C5aR antagonist
C5a hexapeptide
C5aR antagonist
Peptide with aromatic
substistutions (C089)
C5aR
C5aR antagonist
C3a terminus
C3aR antagonist
PR226 peptide
C3b based phage display screening C3
CH2 domain of human IgG
C1q
C3 convertase
Factor B related hexapeptides
Factor D
C1q B chain helical region
C1q
C3
C3
CBP2 peptide
K76
Factor D
K76
Factor D
K76 analogs and derivatives
K76
Factor D
BCX-1470 (analog)
Nafamstat mesilate
Classical and alternate
pathway
TKIXc (derivative)
Oligodeoxy ribonucleotide
Classical and alternate
pathway
K 76 COOH
FUT-175
PS-oligo
B.C. Bhavya and M. Haridas