1346623-17-3
1346623-17-3 structure
- Name: Avacopan
- Chemical Name: ethyl (2R,3S)-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methyl-benzoyl)piperidine-3-carboxylate
- CAS Number: 1346623-17-3
- Molecular Formula: C33H35F4N3O2
- Molecular Weight: 581.64400
- Catalog: Signaling Pathways Immunology/Inflammation Complement System
- Create Date: 2018-06-08 08:11:15
- Modify Date: 2024-01-04 04:40:09
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Avacopan (CCX168) is a potent, selective and orally available complement 5a receptor inhibitor with an IC50 of 0.1 nM.
| Name | ethyl (2R,3S)-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methyl-benzoyl)piperidine-3-carboxylate |
|---|---|
| Synonyms |
(2R,3S)-2-(4-Cyclopentylaminophenyl)-1-(2-fluoro-6-methylbenzoyl)piperidine-3-carboxylic acid (4-methyl-3-trifluoromethylphenyl)amide
Avacopan |
| Description | Avacopan (CCX168) is a potent, selective and orally available complement 5a receptor inhibitor with an IC50 of 0.1 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 0.1 nM (complement 5a receptor )[1] |
| In Vitro | CCX168 displaces [125I]-C5a binding to C5aR on a human myeloid cell line (U937) with a potency (IC50) of 0.1 nM. CCX168 inhibits C5a-mediated chemotaxis of U937 cells with a potency (the concentration of CCX168 that produces a 2-fold right-shift in C5a activity) of 0.2 nM. CCX168 competitively and selectively blocked C5a-induced calcium mobilization in purified human neutrophils, with an IC50 value of 0.2 nM. CCX168 inhibited C5a-induced release of reactive-oxygen species from isolated neutrophils, and is able to completely block respiratory burst in these neutrophils[1]. |
| In Vivo | CCX168 is shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. 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[1]. Oral CCX168, 30 mg/kg daily, reduces the severity of anti-MPO NCGN in hC5aR mice. Glomerular crescents are reduced from 30.4% to 3.3% with CCX168. Urine hematuria, proteinuria, and leukocyturia are reduced in mice receiving CCX168, 30 mg/kg per day. The protection by CCX168 results in reduced crescents and necrosis[2]. |
| Animal Admin | Mice: Human C5aR knock-in mice are dosed with vehicle (PEG-400/solutol-HS15 70:30, 5 mL/kg) or CCX168 by oral gavage. One hour after dosing, C5a (20 μg/kg, 0.1 mL dose volume) is injected intravenously and blood samples collected from retro-orbital eye bleeds. Blood leukocyte levels are analyzed by flow cytometry[1]. |
| References |
| Molecular Formula | C33H35F4N3O2 |
|---|---|
| Molecular Weight | 581.64400 |
| Exact Mass | 581.26700 |
| PSA | 61.44000 |
| LogP | 8.13190 |
| Storage condition | 2-8℃ |