VERCIRNON

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H21ClN2O4S
Molecular Weight	444.931
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC2=C(C=C(Cl)C=C2)C(=O)C3=CC=[N+]([O-])C=C3

InChI

InChIKey=JRWROCIMSDXGOZ-UHFFFAOYSA-N

InChI=1S/C22H21ClN2O4S/c1-22(2,3)16-4-7-18(8-5-16)30(28,29)24-20-9-6-17(23)14-19(20)21(26)15-10-12-25(27)13-11-15/h4-14,24H,1-3H3

HIDE SMILES / InChI

Molecular Formula	C22H21ClN2O4S
Molecular Weight	444.931
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800016003
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27926729 | https://www.ncbi.nlm.nih.gov/pubmed/20660125 | https://www.ncbi.nlm.nih.gov/pubmed/20582872

Vercirnon (GSK-1605786, CCX-282, nTraficet-EN) is a selective, and potent antagonist of human CCR9. Vercirnon binds to the intracellular side of the receptor, exerting allosteric antagonism and preventing G-protein coupling. CCR9 is a tissue-specific lymphocyte trafficking molecule that selectively attracts both B- and T-cells to the small gut. Inhibition of CCR9 by GSK-1605786 may inhibit B- and T-cell entry to the small gut and ameliorate inflammation while leaving immune function at other anatomical sites unaffected. Vercirnon is an orally bioavailable, anti-inflammatory agent that is being developed by ChemoCentryx for treatment of inflammatory bowel disease with an initial focus in Crohn's disease. A pivotal phase III programme of vercirnon was initiated in patients with moderate-to-severe Crohn's disease, however, the programme was suspended when the first pivotal trial failed to meet its primary endpoint. Phase II trials for ulcerative colitis and celiac disease were conducted, however investigations for ulcerative colitis were suspended while no further development has been reported for celiac disease.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
C-C chemokine receptor type 9 2 Target ID: CHEMBL5815 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27926729 \| https://www.ncbi.nlm.nih.gov/pubmed/20660125	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Crohn's disease 42 Sources: http://adisinsight.springer.com/drugs/800016003	Primary	Phase III 656	Unknown Approved Use Unknown
Celiac disease 2 Sources: http://adisinsight.springer.com/drugs/800016003	Primary	Phase II 1132	Unknown Approved Use Unknown
Ulcerative colitis 123 Sources: http://adisinsight.springer.com/drugs/800016003	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
993.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27121943/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		VERCIRNON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
14929 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27121943/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		VERCIRNON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
16.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27121943/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		VERCIRNON plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00FCHV	https://www.1pchem.com/search?query=1P00FCHV
AbovChem LLC	HY-15724
Axon MedChem	2685	https://www.axonmedchem.com/product/2685
BLD Pharm	BD630829	http://www.bldpharm.com/search/Search.html?keyword=BD630829
Chem Scene	CS-4963	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4963
MedChem Express	HY-15724	https://www.medchemexpress.com/search.html?q=HY-15724&ft=&fa=&fp=
MolPort	MolPort-044-649-815	https://www.molport.com/shop/molecule-link/MolPort-044-649-815
MolPort	MolPort-046-426-260	https://www.molport.com/shop/molecule-link/MolPort-046-426-260
eMolecules	313089077	https://orderbb.emolecules.com/search/#?query=313089077
eMolecules	72973136	https://orderbb.emolecules.com/search/#?query=72973136

PubMed

Title	Date	PubMed
GSK-1605786, a selective small-molecule antagonist of the CCR9 chemokine receptor for the treatment of Crohn's disease.	2010 Jul	20582872
Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease.	2010 Oct	20660125
A randomized controlled trial of the efficacy and safety of CCX282-B, an orally-administered blocker of chemokine receptor CCR9, for patients with Crohn's disease.	2013	23527300
Vercirnon for the treatment of Crohn's disease.	2013 Jul	23627683
CCR9 antagonism: potential in the treatment of Inflammatory Bowel Disease.	2015	25897254
Randomised clinical trial: vercirnon, an oral CCR9 antagonist, vs. placebo as induction therapy in active Crohn's disease.	2015 Nov	26400458
Intracellular allosteric antagonism of the CCR9 receptor.	2016 Dec 15	27926729

Patents

Sample Use Guides

In Vivo Use Guide

phase III trial for the treatment of Crohn's disease dosage is 500mg once-daily or twice-daily (NCT01277666)

Route of Administration: Oral

In Vitro Use Guide

Vercirnon (CCX282-B) inhibited CCR9-mediated Ca(2+) mobilization and chemotaxis on Molt-4 cells with IC(50) values of 5.4 and 3.4 nM, respectively. In the presence of 100% human serum, CCX282-B inhibited CCR9-mediated chemotaxis with an IC(50) of 33 nM, and the addition of α1-acid glycoprotein did not affect its potency. CCX282-B inhibited chemotaxis of primary CCR9-expressing cells to CCL25 with an IC(50) of 6.8 nM. CCX282-B was an equipotent inhibitor of CCL25-directed chemotaxis of both splice forms of CCR9 (CCR9A and CCR9B) with IC(50) values of 2.8 and 2.6 nM, respectively.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:50:06 GMT 2023` Edited by `admin` on `Fri Dec 15 15:50:06 GMT 2023`
Record UNII	MWI54OUA12
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VERCIRNON

Official Name

English

CCX-282-B

Code

English

Vercirnon [WHO-DD]

Common Name

English

vercirnon [INN]

Common Name

English

GSK-1605786

Code

English

GSK1605786

Code

English

VERCIRNON [USAN]

Common Name

English

BENZENESULFONAMIDE, N-(4-CHLORO-2-((1-OXIDO-4-PYRIDINYL)CARBONYL)PHENYL)-4-(1,1-DIMETHYLETHYL)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C63817