Avacopan  (Synonyms: CCX168)

Avacopan (CCX168) is a potent, selective and orally available complement 5a receptor (C5aR) inhibitor with an IC₅₀ of 0.1 nM.

IC50: 0.1 nM (complement 5a receptor )^[1]

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

581.64

C₃₃H₃₅F₄N₃O₂

1346623-17-3

Solid

White to off-white

O=C([C@@H]1[C@H](C2=CC=C(NC3CCCC3)C=C2)N(C(C4=C(C)C=CC=C4F)=O)CCC1)NC5=CC=C(C)C(C(F)(F)F)=C5

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.