C5a anaphylatoxin chemotactic receptor 1 (C5aR1) antagonist: treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
File(s)
Accepted version
Author(s)
Pease, JE
Type
Journal Article
Abstract
Inflammation is a key component of several clinically
important disorders, with the recruitment of neutrophils often
pivotal to the inflammatory process. Enzymatic activation
of the complement cascade results in generation of the
complement fragment C5a, a potent chemoattractant for
neutrophils. C5a functions by binding to 2 specific G proteincoupled receptors named C5aR1 and C5aR2 on the surface
of neutrophils and drives cell activation and migration.
Avacopan (CCX-168) is a small molecule antagonist of C5aR1
which was developed by ChemoCentryx. Avacopan binds
with nanomolar affinity to C5aR1 and is a potent inhibitor of
neutrophil recruitment in vitro and in vivo. Avacopan appears
to be well tolerated and in a phase III trial involving individuals
with anti-neutrophil cytoplasmic antibody (ANCA)-induced
vasculitis, blockade of C5aR1 by avacopan was reported to
be efficacious in sparing high levels of glucocorticoid usage,
providing a potential alternative protocol for the treatment
of relapses.
important disorders, with the recruitment of neutrophils often
pivotal to the inflammatory process. Enzymatic activation
of the complement cascade results in generation of the
complement fragment C5a, a potent chemoattractant for
neutrophils. C5a functions by binding to 2 specific G proteincoupled receptors named C5aR1 and C5aR2 on the surface
of neutrophils and drives cell activation and migration.
Avacopan (CCX-168) is a small molecule antagonist of C5aR1
which was developed by ChemoCentryx. Avacopan binds
with nanomolar affinity to C5aR1 and is a potent inhibitor of
neutrophil recruitment in vitro and in vivo. Avacopan appears
to be well tolerated and in a phase III trial involving individuals
with anti-neutrophil cytoplasmic antibody (ANCA)-induced
vasculitis, blockade of C5aR1 by avacopan was reported to
be efficacious in sparing high levels of glucocorticoid usage,
providing a potential alternative protocol for the treatment
of relapses.
Date Issued
2021-03
Date Acceptance
2020-11-26
Citation
Drugs of the Future, 2021, 46 (3), pp.183-190
ISSN
0377-8282
Publisher
Prous Science
Start Page
183
End Page
190
Journal / Book Title
Drugs of the Future
Volume
46
Issue
3
Copyright Statement
Copyright © 2021 Clarivate Analytics
Identifier
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Subjects
ANCA-associated vasculitis
Avacopan
BINDING
C3A
C4A
C5a receptor
C5aR1 inhibitor
C5L2
CCX-168
CHEMOTACTIC RESPONSE
DAMAGE
Life Sciences & Biomedicine
NOMENCLATURE
Pharmacology & Pharmacy
RECEPTOR
Science & Technology
VASCULITIDES
Publication Status
Published
Date Publish Online
2021-03