Delving into the Latest Updates on Vicriviroc with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

SCH-D, Schering-D, Vicriviroc maleate (USAN)

+ [4]

Target

CCR5

Mechanism

CCR5 antagonists(C-C chemokine receptor type 5 antagonists), Virus internalization inhibitors

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases+ [2]

Active Indication-

Inactive Indication

Acquired Immunodeficiency SyndromeColorectal CancerHIV Infections

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck GmbH

Merck Sharp & Dohme Corp.

Merck & Co., Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC28H38F3N5O2

InChIKeyCNPVJJQCETWNEU-CYFREDJKSA-N

CAS Registry306296-47-9

BACKGROUNDPembrolizumab, a monoclonal antibody against PD-1, has shown limited efficacy in patients with microsatellite stable or mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (CRC). We evaluated vicriviroc (small-molecule C-C motif chemokine ligand 5 antagonist) plus pembrolizumab in patients with advanced or metastatic MSS/pMMR CRC.PATIENTS AND METHODSThis open-label, phase 2 trial (NCT03631407) enrolled adults with histologically confirmed, locally advanced, unresectable or metastatic CRC that was MSS per local assessment. All patients had received previous treatment with standard therapies. Patients were randomized 1:1 to vicriviroc 150 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or vicriviroc 250 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles (2 years). Primary endpoints were the objective response rate (ORR) as assessed by the investigator per RECIST v1.1, dose-limiting toxicities (DLTs), adverse events (AEs), and discontinuations due to AEs.RESULTSForty patients were enrolled and treated. ORR was 5% (95% CI, 0.1%-24.9%) in both treatment groups. There were no complete responses; 1 patient in each treatment group experienced a partial response. No patient in the vicriviroc 150 mg plus pembrolizumab group experienced a DLT. Two patients in the vicriviroc 250 mg plus pembrolizumab group experienced DLTs (1 grade 4 encephalopathy and 1 grade 4 pneumonitis).CONCLUSIONThe combination of vicriviroc at doses of 150 or 250 mg plus pembrolizumab 200 mg showed limited antitumor activity in patients with advanced or metastatic MSS/pMMR CRC. Toxicity with the combination was manageable.

08 Sep 2023·Cells

The Role and Therapeutic Targeting of CCR5 in Breast Cancer.

Review

Author: Ashton, Anthony W ; Mahal, Amanpreet S ; Jiao, Xuanmao ; Alaziz, Mustafa ; Halama, Niels ; Jaeger, Dirk ; Pestell, Richard G ; Hamid, Rasha

The G-protein-coupled receptor C-C chemokine receptor 5 (CCR5) functions as a co-receptor for the entry of HIV into immune cells. CCR5 binds promiscuously to a diverse array of ligands initiating cell signaling that includes guided migration. Although well known to be expressed on immune cells, recent studies have shown the induction of CCR5 on the surface of breast cancer epithelial cells. The function of CCR5 on breast cancer epithelial cells includes the induction of aberrant cell survival signaling and tropism towards chemo attractants. As CCR5 is not expressed on normal epithelium, the receptor provides a potential useful target for therapy. Inhibitors of CCR5 (CCR5i), either small molecules (maraviroc, vicriviroc) or humanized monoclonal antibodies (leronlimab) have shown anti-tumor and anti-metastatic properties in preclinical studies. In early clinical studies, reviewed herein, CCR5i have shown promising results and evidence for effects on both the tumor and the anti-tumor immune response. Current clinical studies have therefore included combination therapy approaches with checkpoint inhibitors.

01 Jan 2023·Vitamins and hormones

Structural dynamics of chemokine receptors.

Article

Author: Akhter, Sana ; Miao, Yinglong ; Pawnikar, Shristi

Membrane proteins such as G protein-coupled receptors (GPCRs) are involved in awide range of physiological and pathological cellular processes. Binding of extracellular signals to GPCRs, including hormones, neurotransmitters, peptides and proteins, can activate intracellular signaling cascades via G protein interaction. Chemokine receptors are key GPCRs implicated in cancers, immune responses, cell migration and inflammation. Specifically, the CCR5 and CXCR4 chemokine receptors serve as important therapeutic targets against Human Immunodeficiency virus (HIV) entry into human cells. Maraviroc and Vicriviroc, two clinically used HIV entry inhibitors, are antagonists of the CCR5 receptor. These drugs block HIV entry, but ultimately resistance develops, due to emergence of viruses that can utilize the CXCR4 co-receptor. Unfortunately, development of chemokine receptor antagonists as selective drugs of HIV infection has been greatly hindered as their target orthosteric site is conserved among different receptor subtypes. Accordingly, it is important to understand the structural dynamics of these receptors to develop more effective therapeutics. In this chapter, we describe the latest advances in studies of these two key chemokine receptors with respect to their structures, dynamics and function.

1

News (Medical) associated with Vicriviroc

08 Feb 2023

·www.biospace.com

Infectious disease specialist Dr. Regis A. Vilchez is appointed CMO of MicuRx Pharmaceuticals, Inc.

SHANGHAI, Feb. 8, 2023 /PRNewswire/ -- Shanghai MicuRx Pharmaceutical Co., Ltd. ("MicuRx," 688373) announced recently that it has appointed Regis A. Vilchez, MD, PhD, an experienced R&D biopharmaceutical executive and infectious disease expert, as Chief Medical Officer of its American subsidiary, MicuRx Pharmaceuticals, Inc. He oversees new drug development programs and clinical activities in the United States, Europe and other regions. Dr. Vilchez earned an M.D. from the Universidad Autónoma de Centro América in Costa Rica and a Ph.D. from Baylor College of Medicine in Houston, Texas, the United States. He completed an internal medicine residency at Robert Wood Johnson Medical School, a clinical infectious diseases fellowship at the University of Pittsburgh, and a molecular virology fellowship at Baylor College of Medicine. Prior to entering the biopharmaceutical industry, Dr. Vilchez was full time faculty in the Departments of Medicine and Molecular Virology & Microbiology at Baylor College of Medicine. Dr. Vilchez has served in multiple R&D roles at Boehringer Ingelheim, Merck, Roche, Abbott/AbbVie, Mallinckrodt Pharmaceuticals and other smaller biotechnology companies. In those roles, Dr. Vilchez has been a key contributor to the global development of new therapies such as Vicriviroc, Victrelis, Viekirax, Technivie, Ocaliva, Terlivaz, and StrataGraft. Dr. Vilchez has co-authored more than 100 peer-reviewed scientific publications in high impact biomedical journals such as the New England Journal of Medicine, The Lancet, and Clinical Microbiology Reviews. The leadership of Dr. Vilchez will enhance MicuRx's global R&D programs and clinical activities. MicuRx is rapidly expanding its business and assembling an international expert team with extensive experience and an innovative spirit to develop a robust global R&D organization. Moving forward, MicuRx will remain focused on advancing its anti-infective product pipeline, and provide more effective and safer treatment options for patients around the world. View original content to download multimedia: SOURCE MicuRx Pharmaceuticals Company Codes: Shanghai:688373, Shanghai:688373.SS

Executive Change

100 Deals associated with Vicriviroc

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External Link

KEGG	Wiki	ATC	Drug Bank
D06297	Vicriviroc	-	DB06652

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 3	CA	Merck Sharp & Dohme Corp.	24 Sep 2018
Colorectal Cancer	Phase 3	US	Merck & Co., Inc.	24 Sep 2018
Acquired Immunodeficiency Syndrome	Phase 3	-	Merck Sharp & Dohme Corp.	01 Sep 2005
HIV Infections	Phase 3	AU	Merck GmbH	-
HIV Infections	Phase 3	-	Merck GmbH	-
HIV Infections	Phase 3	CA	Merck GmbH	-
HIV Infections	Phase 3	US	Merck GmbH	-
HIV Infections	Phase 3	-	Merck GmbH	-
HIV Infections	Phase 3	ZA	Merck GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03631407 (7690-046 \| MK-7690-046, CTgov)	Phase 2	Metastatic Microsatellite Stable Colorectal Carcinoma	41	Vicriviroc+pembrolizumab (Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg))	mcjaffnkak(nfvcwejlgz) = xcpxiwpeis nupzdyfdom (mywvhldahg, zxaddrykwx - zqyghwjtss) View more	-	07 Jun 2022
				Vicriviroc+pembrolizumab (Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg))	mcjaffnkak(nfvcwejlgz) = fbpjykmpno nupzdyfdom (mywvhldahg, tumcvrzzjc - chpzldtqci) View more
NCT00243230 (MK-7690-020 \| VICTOR-E1 \| P03672, CTgov)	Phase 2	HIV Infections	116	Vicriviroc (Double-Blind Period - Vicriviroc 30 mg Plus an ART Regimen)	fsydeoaoom(bhiqrseazr) = zbufuhohlo lenxtpdbaw (qtgzpmdvyt, kwkxdfbfzg - htakylpusw) View more	-	08 Jun 2021
				Vicriviroc (Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen)	fsydeoaoom(bhiqrseazr) = jkoxapvpci lenxtpdbaw (qtgzpmdvyt, iiwtuisbwm - vzurhkqdeb) View more
NCT00686829 (A5211 \| P04100, CTgov)	Phase 2	HIV Infections	79	Vicriviroc maleate	ykmvxnjpnr(ytufqapboy) = xkpowmvlns hkmmclrmzf (ckhustiign, eoiaqigoxs - jskfnhndwg) View more	-	03 Dec 2020
NCT00474370 \| NCT00523211 (VICTOR-E3, VICTOR-E4, Pubmed \| J Infect)	Phase 3	HIV Infections	-	Vicriviroc 30 mg QD	(rgqiorlixu) = zbzsgjizaw ybfhtcbthc (fplxldoqjn ) View more	Negative	01 Oct 2012
				Placebo	(rgqiorlixu) = rvzsqvgsog ybfhtcbthc (fplxldoqjn ) View more
NCT00686829 (A5211, Pubmed)	Phase 2	Peripheral Nervous System Diseases	118	Vicriviroc (pooled doses)	nxvzwtxpmk(tdsjpezinr): OR = 1.52 (95% CI, 0.59 - 3.9), P-Value = 0.39	Negative	28 Feb 2010
				Placebo
NCT00243230 (MK-7690-020 \| P03672, Pubmed \| Am J Trop Med Hyg)	Phase 2	-	116	Vicriviroc 30 mg	phnqwuobdf(xeaccsepol) = xuaidxcrrr mhigqbnneq (wyxkbyrwxl )	-	15 Feb 2010
				Vicriviroc 20 mg	phnqwuobdf(xeaccsepol) = jodqjnqgti mhigqbnneq (wyxkbyrwxl )
ACTG 5211 (IAS2008)	Not Applicable	-	79	Vicriviroc 15 mg	buymuooqzc(xhgqaxvfsl) = Hodgkin´s disease (previously reported in Gulick, JID 2007) opictajrgq (vsumsbgorg ) View more	-	01 Jan 2008
ACTG 5211 (IAS2007)	Not Applicable	HIV Infections	118	Vicriviroc 10 mg	(zjdxtsqbyb) = were similar across arms egumwbdfsn (kcpzlnlfew ) View more	-	01 Jan 2007
				Vicriviroc 15 mg
VICTOR-E1 (IAS2007)	Not Applicable	HIV Infections	116	vicriviroc 20mg	(mwrsauhkuh) = xrcfixbriv rddslobdfv (twjepszjtj ) View more	-	01 Jan 2007