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
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
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 |
DescriptionSources: http://adisinsight.springer.com/drugs/800016003Curator'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
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.
Approval Year
Cmax
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 |
T1/2
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 |
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 |
|
Characterization of CCX282-B, an orally bioavailable antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. | 2010 Oct |
|
CCR9 antagonism: potential in the treatment of Inflammatory Bowel Disease. | 2015 |
|
Randomised clinical trial: vercirnon, an oral CCR9 antagonist, vs. placebo as induction therapy in active Crohn's disease. | 2015 Nov |
|
Intracellular allosteric antagonism of the CCR9 receptor. | 2016 Dec 15 |
Sample Use Guides
In Vivo Use Guide
Sources: http://adisinsight.springer.com/drugs/800016003
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20660125
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
Edited
Fri Dec 15 15:50:06 GMT 2023
by
admin
on
Fri Dec 15 15:50:06 GMT 2023
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Record UNII |
MWI54OUA12
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Record Status |
Validated (UNII)
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C63817
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SUB119260
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
BINDING
IC50
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TARGET -> INHIBITOR |
Migration assay in serum
BIOASSAY (CELLULAR)
IC50
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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