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Details

Stereochemistry ABSOLUTE
Molecular Formula C33H35F4N3O2
Molecular Weight 581.6447
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVACOPAN

SMILES

Cc1ccc(cc1C(F)(F)F)N=C([C@@]2([H])CCCN([C@@]2([H])c3ccc(cc3)NC4CCCC4)C(=O)c5c(C)cccc5F)O

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
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P21730
Gene ID: 728.0
Gene Symbol: C5AR1
Target Organism: Homo sapiens (Human)
0.1 nM [IC50]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
359 ng/mL
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AVACOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
197 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVACOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13000 ng × h/mL
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AVACOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2030 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVACOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
120 h
50 mg 2 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
AVACOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
64 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVACOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg single, oral
Highest studied dose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources: Page: p.9
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.9
50 mg 2 times / day multiple, oral
Studied dose
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.9
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.9
PubMed

PubMed

TitleDatePubMed
C5a receptor (CD88) blockade protects against MPO-ANCA GN.
2014 Feb
Patents

Patents

Sample Use Guides

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
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.
Name Type Language
AVACOPAN
INN   USAN  
INN   USAN  
Official Name English
AVACOPAN [USAN]
Common Name English
AVACOPAN [INN]
Common Name English
CCX168
Code English
CCX-168
Code English
3-PIPERIDINECARBOXAMIDE, 2-(4-(CYCLOPENTYLAMINO)PHENYL)-1-(2-FLUORO-6-METHYLBENZOYL)-N-(4-METHYL-3-(TRIFLUOROMETHYL)PHENYL)-, (2R,3S)-
Systematic Name English
(2R,3S)-2-(4-(CYCLOPENTYLAMINO)PHENYL)-1-(2-FLUORO-6-METHYLBENZOYL)-N-(4-METHYL-3-(TRIFLUOROMETHYL)PHENYL)PIPERIDINE-3-CARBOXAMIDE
Systematic Name English
AVACOPAN [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 443714
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
FDA ORPHAN DRUG 559016
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
EU-Orphan Drug EU/3/14/1373
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
FDA ORPHAN DRUG 432014
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
Code System Code Type Description
PUBCHEM
49841217
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
PRIMARY
NCI_THESAURUS
C174788
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
PRIMARY
CAS
1346623-17-3
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545099
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
PRIMARY
DRUG BANK
DB15011
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
PRIMARY
FDA UNII
O880NM097T
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
PRIMARY
INN
10211
Created by admin on Sat Jun 26 05:27:19 UTC 2021 , Edited by admin on Sat Jun 26 05:27:19 UTC 2021
PRIMARY