Avacopan (CCX168) is a first-in-class, potent, selective and orally available complement 5a receptor (C5aR1 or CD88) antagonist with an IC50 of 0.1 nM.
Avacopan (CCX168) blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. Avacopan competitively and selectively blocked C5a-induced calcium mobilization in purified human neutrophils, with an IC50 value of 0.2 nM.
In vivo, in mice dosed orally with 0.03 mg/kg of CCX168, the resulting plasma CCX168 concentration of 15 nM (8.7 ng/mL) reduces the drop in circulating leukocytes from 53% to 25%. In mice administered 0.3 mg/kg of CCX168, the resulting plasma CCX168 concentration of 75 nM (44 ng/mL) reduces the drop in circulating leukocytes from 53% to only 10% relative to baseline (p<0.05 for CCX168 vs. vehicle control). Oral doses of CCX168 of either 3 or 30 mg/kg completely blocks C5a-induced leukopenia in hC5aR knock-in mice.
Exp Ther Med. 2022 Jun 7;24(2):493.
The complement C3a-C3aR and C5a-C5aR pathways promote viability and inflammation of human retinal pigment epithelium cells by targeting NF-κB signaling
Avacopan purchased from AbMole
Molecular Weight | 581.64 |
Formula | C33H35F4N3O2 |
CAS Number | 1346623-17-3 |
Solubility (25°C) | DMSO ≥ 9 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[2] Xiao H, et al. J Am Soc Nephrol. C5a receptor (CD88) blockade protects against MPO-ANCA GN.
Related Complement System Products |
---|
P014
P014 is a C5 antibody/CFH fragment fusion protein that can be used in studies related to paroxysmal sleep hemoglobinuria (PNH) and thrombotic microangiopathy (TMA). |
POT-4
POT-4 (AL-78898A), a Compstatin derivative, is a potent inhibitor of complement factor C3 activation. |
TLQP-21
TLQP-21, a VGF-derived peptide endowed of endocrine and extraendocrine properties, is a potent G-protein-coupled receptor complement-3a receptor 1 (C3aR1) agonist (EC50: mouse TLQP-21=10.3 μM; human TLQP-21=68.8 μM). |
N-((Allyloxy)carbonyl)-N-methyl-L-alanine
N-((Allyloxy)carbonyl)-N-methyl-L-alanine is a Alanine derivative. |
C5a Receptor agonist, mouse, human
C5a Receptor agonist, mouse, human is a biological active peptide. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.