Navarixin

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H23N3O5.H2O
Molecular Weight	415.4397
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.CC[C@@H](NC1=C(NC2=CC=CC(C(=O)N(C)C)=C2O)C(=O)C1=O)C3=CC=C(C)O3

InChI

InChIKey=AFTCWZSEWTXWTL-BTQNPOSSSA-N

InChI=1S/C21H23N3O5.H2O/c1-5-13(15-10-9-11(2)29-15)22-16-17(20(27)19(16)26)23-14-8-6-7-12(18(14)25)21(28)24(3)4;/h6-10,13,22-23,25H,5H2,1-4H3;1H2/t13-;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800022619 | https://www.ncbi.nlm.nih.gov/pubmed/17181143 | https://www.ncbi.nlm.nih.gov/pubmed/17496166https://www.ncbi.nlm.nih.gov/pubmed/17181143 | https://www.ncbi.nlm.nih.gov/pubmed/26271598

Navarixin (SCH 527123) is an oral antagonist of CXC receptors 1 and 2. The drug is currently under Phase II trial for the treatment of psoriasis, COPD and asthma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Interleukin-8 receptor B 10 Target ID: CHEMBL2434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17496166	Antagonist 2849	0.97 nM [IC50]
Interleukin-8 receptor A 3 Target ID: CHEMBL4029 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17496166	Antagonist 2849	43.0 nM [IC50]
C-X-C chemokine receptor type 1 2 Target ID: P25024\|\|\|Q6IN95 Gene ID: 3577.0 Gene Symbol: CXCR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17181143	Antagonist 2849	36.0 nM [IC50]
C-X-C chemokine receptor type 2 3 Target ID: P25025 Gene ID: 3579.0 Gene Symbol: CXCR2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17181143	Antagonist 2849	2.6 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic obstructive pulmonary disease 175 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25695403	Palliative	Phase II 1147	Unknown Approved Use Unknown
Asthma 244 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00688467	Palliative	Phase II 1147	Unknown Approved Use Unknown
Psoriasis 87 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00684593	Palliative	Phase II 1147	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19643947/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19643947/	Other AEs: Neutropenia, Headache... Other AEs: Neutropenia (grade 1-2, 36.8%) Headache (10.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/19643947/
30 mg 1 times / day multiple, oral Studied dose Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27640067/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27640067/	Other AEs: Neutropenia... Other AEs: Neutropenia (15.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/27640067/

AEs

AE	Significance	Dose	Population
Headache	10.5%	50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19643947/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19643947/
Neutropenia	grade 1-2, 36.8%	50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19643947/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19643947/
Neutropenia	15.8%	30 mg 1 times / day multiple, oral Studied dose Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27640067/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27640067/

PubMed

Title	Date	PubMed
Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation.	2015-10	26271598
CXCR2 Antagonist MK-7123. A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease.	2015-05-01	25695403
International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors.	2014	24218476
The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models.	2012-06	22391039
Small-molecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival, and angiogenesis.	2009-04-01	19293256
Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2 antagonist.	2007-08	17496166
A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation.	2007-08	17496165
Future therapeutic treatment of COPD: struggle between oxidants and cytokines.	2007	18229560
Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist.	2006-12-28	17181143

Patents

Sample Use Guides

In Vivo Use Guide

Psoriasis: Navarixin 30 mg administered orally once daily for 28 days.

Route of Administration: Oral

In Vitro Use Guide

Navarixin is a potent, allosteric antagonist of both CXCR1 and CXCR2, with Kd values of 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, 0.08 nM for mouse, rat and cynomolgus monkey CXCR2, respectivelly.

Name

Type

Language

MK-7123 MONOHYDRATE

Preferred Name

English

Navarixin

Official Name

English

2-hydroxy-N,N-dimethyl-3-[(2-{[(1R)-1-(5-methylfuran-2-yl)propyl]amino}-3,4-dioxocyclobut-1-enyl)amino]benzamide monohydrate

Systematic Name

English

PS291822

Code

English

SCH-527123 MONOHYDRATE

Code

English

PS-291822

Code

English

Benzamide, 2-hydroxy-N,N-dimethyl-3-[[2-[[(1R)-1-(5-methyl-2-furanyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]-, hydrate (1:1)

Systematic Name

English

NAVARIXIN [USAN]

Common Name

English

Navarixin monohydrate

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID20235453