AVACOPAN

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 Search

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

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27768695 | http://www.chemocentryx.com/pipeline/orphan-and-rare-diseases/

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
C5a anaphylatoxin chemotactic receptor 1 1 Target ID: P21730 Gene ID: 728.0 Gene Symbol: C5AR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27768695	Antagonist 2778		0.1 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Anti-neutrophil cytoplasmic antibody-associated vasculitis 1 Sources: http://www.chemocentryx.com/pipeline/orphan-and-rare-diseases/	Primary	Phase III 656	Unknown Approved Use Unknown
Immunoglobulin A nephropathy 1 Sources: http://adisinsight.springer.com/drugs/800031548	Primary	Phase II 1132	Unknown Approved Use Unknown
Atypical hemolytic uremic syndrome 1 Sources: http://www.chemocentryx.com/pipeline/orphan-and-rare-diseases/	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
359 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27768695	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27768695	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

Value	Dose	Co-administered	Analyte	Population
13000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27768695	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27768695	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
120 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27768695	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27768695	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

Dose	Population	Adverse events
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27768695 Page: p.9	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/27768695 Page: p.9	Sources: https://pubmed.ncbi.nlm.nih.gov/27768695 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: https://pubmed.ncbi.nlm.nih.gov/27768695 Page: p.9	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/27768695 Page: p.9	Sources: https://pubmed.ncbi.nlm.nih.gov/27768695 Page: p.9

Sourcing

Vendor/Aggregator	ID	URL
AbovChem LLC	HY-17627	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-17627
ChemShuttle	183272	https://www.chemshuttle.com/catalogsearch/result/?q=183272
Hairui	AVSA082	http://www.hairuichem.com/en/product/search.do?q=AVSA082
Molnova	M11405	https://www.molnova.com/en/serch-list.html?keywords=M11405
MuseChem	I003297	https://www.musechem.com/product/I003297.html
eMolecules	89941043	https://orderbb.emolecules.com/search/#?query=89941043
mcule	MCULE-2769065669	https://mcule.com/MCULE-2769065669/

PubMed

Title	Date	PubMed
C5a receptor (CD88) blockade protects against MPO-ANCA GN.	2014 Feb	24179165
Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.	2016	27768695
Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis.	2017 Sep	28400446

Patents

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 Created by `admin` on `Sat Dec 16 11:10:05 GMT 2023` Edited by `admin` on `Sat Dec 16 11:10:05 GMT 2023`
Record UNII	O880NM097T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AVACOPAN

Official Name

English

AVACOPAN [USAN]

Common Name

English

avacopan [INN]

Common Name

English

AVACOPAN [JAN]

Common Name

English

Avacopan [WHO-DD]

Common Name

English

AVACOPAN [ORANGE BOOK]

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

Classification Tree Code System Code

FDA ORPHAN DRUG

443714