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Details

Stereochemistry ABSOLUTE
Molecular Formula C33H35F4N3O2
Molecular Weight 581.6435
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVACOPAN

SMILES

CC1=CC=C(NC(=O)[C@H]2CCCN([C@H]2C3=CC=C(NC4CCCC4)C=C3)C(=O)C5=C(F)C=CC=C5C)C=C1C(F)(F)F

InChI

InChIKey=PUKBOVABABRILL-YZNIXAGQSA-N
InChI=1S/C33H35F4N3O2/c1-20-12-15-25(19-27(20)33(35,36)37)39-31(41)26-10-6-18-40(32(42)29-21(2)7-5-11-28(29)34)30(26)22-13-16-24(17-14-22)38-23-8-3-4-9-23/h5,7,11-17,19,23,26,30,38H,3-4,6,8-10,18H2,1-2H3,(H,39,41)/t26-,30-/m0/s1

HIDE SMILES / InChI
Molecular Formula C33H35F4N3O2
Molecular Weight 581.6435
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Avacopan (CCX-168) an orally administered selective and potent complement 5a receptor inhibitor. Avacopan blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. Avacopan is being developed for inflammatory and autoimmune diseases.

Originator

ChemoCentryx
3

Approval Year

2021
470

Targets

Primary TargetPharmacologyConditionPotency
C5a anaphylatoxin chemotactic receptor 1
1
Antagonist
2,778
 0.1 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Anti-neutrophil cytoplasmic antibody-associated vasculitis
1
 Primary
Phase III
656
Unknown
Immunoglobulin A nephropathy
1
 Primary
Phase II
1,132
Unknown
Atypical hemolytic uremic syndrome
1
 Primary
Phase II
1,132
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
359 ng/mL
50 mg 2 times / day steady-state, oral
 AVACOPAN plasma
Homo sapiens
197 ng/mL
100 mg single, oral
 AVACOPAN plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
13000 ng × h/mL
50 mg 2 times / day steady-state, oral
 AVACOPAN plasma
Homo sapiens
2030 ng × h/mL
100 mg single, oral
 AVACOPAN plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
120 h
50 mg 2 times / day steady-state, oral
 AVACOPAN plasma
Homo sapiens
64 h
100 mg single, oral
 AVACOPAN plasma
Homo sapiens

Doses

PubMed

Patents

US9745268
1

Sample Use Guides

In Vivo Use Guide
CCX168 was 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 a randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone.
Route of Administration: Oral
In Vitro Use Guide
Addition of CCX168 to U937 cells in a calcium mobilization assay inhibited C5a with a potency (A2) of 0.1 nM. CCX168 competitively and selectively blocked C5a-induced calcium mobilization in purified human neutrophils, with an IC50 value of 0.2 nM.
Substance Class Chemical
Record UNII
O880NM097T
Record Status Validated (UNII)
Record Version
NIH
NCATS
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