Delving into the Latest Updates on Vercirnon Sodium with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Traficet-EN, Vercirnon

+ [7]

Target

CCR9

Mechanism

CCR9 antagonists(C-C chemokine receptor type 9 antagonists)

Therapeutic Areas

Immune System DiseasesDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Celiac DiseaseCrohn Disease

Originator Organization

ChemoCentryx, Inc.

Active Organization-

Inactive Organization

GSK Plc

ChemoCentryx, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC22H21ClN2NaO4S

InChIKeyQFAUJPTYAGADMS-UHFFFAOYSA-N

CAS Registry886214-18-2

View All Structures (2)

This is an open-label, parallel group, single and repeat dose pharmacokinetic (PK) study in healthy male and female subjects. This study will confirm the PK and safety profile in Chinese subjects. GSK1605786 is currently in clinical development for the treatment of Crohn's disease. Subjects will receive one of two GSK1605786 doses (500 mg once daily or 500mg twice daily) within 30 minutes after a meal. The study will consist of single and repeat dose sessions, with pre-dose and serial PK samples taken up to 72-h post-dose.

Start Date27 May 2013

Sponsor / Collaborator

GSK Plc

EUCTR2010-022382-10-SK / Not yet recruitingNot Applicable

A Randomised, Double-blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of GSK1605786A in the Treatment of Subjects with Moderately-to Severely Active Crohn’s Disease

Start Date22 May 2012

Sponsor / Collaborator

GlaxoSmithKline Research & Development Ltd.

EUCTR2011-002818-37-BE / Not yet recruitingPhase 2

A phase II, 20-week, multi-centre, randomised, double-blind, placebo-controlled, parallel group proof of concept study to investigate the efficacy and safety of GSK1605786 for treatment of patients with active Ulcerative Colitis.

Start Date15 Feb 2012

Sponsor / Collaborator

GlaxoSmithKline Research & Development Ltd.

100 Clinical Results associated with Vercirnon Sodium

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100 Translational Medicine associated with Vercirnon Sodium

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100 Patents (Medical) associated with Vercirnon Sodium

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23

Literatures (Medical) associated with Vercirnon Sodium

14 Mar 2022·Angewandte Chemie International Edition

A Chemical Biology Toolbox Targeting the Intracellular Binding Site of CCR9: Fluorescent Ligands, New Drug Leads and PROTACs

Article

Author: Merten, Nicole ; Schiedel, Matthias ; Vogt, Hannah ; Kostenis, Evi ; Wiefhoff, Martin F. J. ; Huber, Max E. ; Toy, Lara ; Budzinski, Julian ; Schmidt, Maximilian F. ; Weikert, Dorothee

AbstractA conserved intracellular allosteric binding site (IABS) has recently been identified at several G protein‐coupled receptors (GPCRs). Starting from vercirnon, an intracellular C−C chemokine receptor type 9 (CCR9) antagonist and previous phase III clinical candidate for the treatment of Crohn's disease, we developed a chemical biology toolbox targeting the IABS of CCR9. We first synthesized a fluorescent ligand enabling equilibrium and kinetic binding studies via NanoBRET as well as fluorescence microscopy. Applying this molecular tool in a membrane‐based setup and in living cells, we discovered a 4‐aminopyrimidine analogue as a new intracellular CCR9 antagonist with improved affinity. To chemically induce CCR9 degradation, we then developed the first PROTAC targeting the IABS of GPCRs. In a proof‐of‐principle study, we succeeded in showing that our CCR9‐PROTAC is able to reduce CCR9 levels, thereby offering an unprecedented approach to modulate GPCR activity.

01 Dec 2020·MetabolismQ1 · MEDICINE

The role of the CCL25-CCR9 axis in beta-cell function: potential for therapeutic intervention in type 2 diabetes

Q1 · MEDICINE

Article

Author: Lee, Vivian ; Huang, Guo Cai ; Atanes, Patricio ; Persaud, Shanta J

BACKGROUND AND PURPOSEChemokines are known to play essential roles mediating immunity and inflammation in many physiological and pathophysiological processes, with reports linking their action to the development of obesity, insulin resistance and type 2 diabetes (T2D). Given our findings of highly upregulated mRNA expression of the chemokine receptor CCR9 in islets from obese human donors, we have determined the effects of CCR9 activation by CCL25 on islet function and viability.BASIC PROCEDURESRT-qPCR was used to measure expression of 384 GPCR mRNAs in human islets from organ donors with normal and elevated BMI. mRNA encoding CCR9, a receptor that was highly upregulated in islets from obese donors, was also quantified in islets from lean and high-fat diet (HFD) mice. The effects of CCR9 activation by exogenous CCL25 in human and mouse islets and its inhibition by the CCR9 antagonist vercirnon on insulin secretion, apoptosis and cAMP accumulation were examined using standard techniques.MAIN FINDINGSThe qPCR analysis showed altered expression of several GPCRs in islets isolated from lean and obese donors. CCR9 displayed over 90-fold upregulation in islets from obese individuals, and it was also significantly upregulated in islets from obese mice. In isolated human and mouse islets exogenous CCL25 inhibited glucose-induced insulin secretion in a concentration-dependent manner, enhanced cytokine-induced apoptosis and significantly reduced forskolin-induced elevation in cAMP levels. These detrimental effects of CCL25 in islets were blocked by vercirnon, which had no effect on its own.PRINCIPAL CONCLUSIONSWe have shown that CCL25 acts via the Gαi-coupled receptor CCR9 to impair beta-cell function by inhibiting insulin secretion and promoting cytokine-induced apoptosis. Upregulation of CCR9 in islets in obesity, possibly secondary to accumulation of passenger immune cells, may predispose to metabolic dysfunction and our data suggest that CCL25 downregulation or CCR9 inhibition could be explored to treat T2D.

01 Feb 2019·Best Practice & Research Clinical GastroenterologyQ3 · MEDICINE

Interfering with leukocyte trafficking in Crohn's disease

Q3 · MEDICINE

Review

Author: Bryant, Robert V ; Travis, Simon ; Biswas, Sujata

The discovery of gut-specific leukocytes and the ability to modulate their function has been a groundbreaking development in the treatment of inflammatory bowel disease. Drugs target the interaction between lymphocytes and endothelial cells via integrins and their ligand cellular adhesion molecules. Safety, efficacy and sustainability of effect are key to this drug class, notwithstanding the association of natalizumab with fatal polyoma virus infection. Vedolizumab (2014) now licensed for the treatment of Crohn's disease around the world provides gut-specific immunosuppression. Targets for modulators of leukocyte trafficking include (examples in brackets) ICAM-1 (alicaforsen, efalizumab); MAdCAM-1 (PF-00547 659); α4 and related receptors (abrilumab, etrolizumab, natalizumab, vedolizumab); chemokine receptor CCR9 (vercirnon); and sphingosine 1-phosphate receptors (etrasimod, fingolimod, ozanimod). Oral and subcutaneous therapies are in development. The safety, efficacy and practice points of licensed drugs are discussed, in addition to initial results from therapeutic trials.

100 Deals associated with Vercirnon Sodium

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15250

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Crohn Disease	Phase 3	FR	GSK Plc	20 Dec 2010
Crohn Disease	Phase 3	BE	GSK Plc	20 Dec 2010
Crohn Disease	Phase 3	FR	GSK Plc	20 Dec 2010
Crohn Disease	Phase 3	US	GSK Plc	20 Dec 2010
Crohn Disease	Phase 3	ES	GSK Plc	20 Dec 2010
Crohn Disease	Phase 3	BE	GSK Plc	20 Dec 2010
Crohn Disease	Phase 3	US	GSK Plc	20 Dec 2010
Crohn Disease	Phase 3	KR	GSK Plc	20 Dec 2010
Crohn Disease	Phase 2	ES	GSK Plc	20 Dec 2010
Crohn Disease	Discovery	KR	GSK Plc	20 Dec 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01277666 (SHIELD-1, CTgov)	Phase 3	Crohn Disease	608	Placebo	dtpnnjejnx(zzazhlqkjy) = kmcowhzkqm ulpwxkfnxy (hgqsrybczi, fusadpvfvs - lmzxzpcamd) View more	-	19 Sep 2017
NCT01318993 (SHIELD-3, CTgov)	Phase 3	Crohn Disease	399	GSK1605786A	olplfkdwmf(bobclbyzaw) = dpvznjbonn hjbbfddbyy (jdnnetbovc, encxhephxw - nyvvklwrzv) View more	-	14 Sep 2017
NCT01316939 (SHIELD-2, CTgov)	Phase 3	Crohn Disease	229	Placebo	yrpfijqqre(kwexajjsgp) = jzunxpvnbg cayeyykzpe (linvbebzvr, ozzsybyygq - ckcsmslrhm) View more	-	07 Sep 2017
NCT01536418 (SHIELD-4, CTgov)	Phase 3	Crohn Disease	255	GSK1605786A (GSK1605786A 500 mg, Once Daily)	rnjxlixmvz(daeblzfsct) = sgwpibgmse blsewoupvb (wmkezrnhuj, nbcumbpajf - djvphlvpvx) View more	-	17 Aug 2017
				GSK1605786A (GSK1605786A 500 mg,Twice Daily)	rnjxlixmvz(daeblzfsct) = yodfaaelbk blsewoupvb (wmkezrnhuj, gistkabjhf - gucwpzviwb) View more
PROTECT-1, SHIELD-1 (UEGW)	Phase 2/3	Crohn Disease CRP \| fecal calprotectin	-	Vercirnon 500 mg QD	ierxbwmtjs(vncearcxuq) = more GI adverse events were found in SHIELD-1, in particular at the highest dose, 500 mg BID, which was not tested in PROTECT-1 hbpnbbxawp (beboaamvft )	Negative	01 Oct 2014
				Vercirnon 500 mg BID
NCT00306215 (Pubmed \| J Biol Chem)	Phase 2	Crohn Disease	436	Placebo	(dsjarxofka) = rfdaxoushm dnztvydlpt (uajnrgbqdn ) View more	-	01 Jan 2013
				CCX282-B 250 mg once daily	(dsjarxofka) = zandaalopc dnztvydlpt (uajnrgbqdn ) View more