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

Action

antagonists, inhibitors

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+ [1]

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck GmbH

Schering-Plough Research Institute

Merck Sharp & Dohme Corp.

+ [1]

License Organization-

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC28H38F3N5O2

InChIKeyCNPVJJQCETWNEU-CYFREDJKSA-N

CAS Registry306296-47-9

Obesity (OB) is a prevalent metabolic disorder. With the advancement of the economy, the prevention and treatment of obesity is a big problem for the global community. The methods to lose weight include exercise, diet, medicine, and surgery. Compared with other methods, diet regulation is safer and more effective. Hawthorn fruit has the effect of reducing weight, but the mechanism of effectiveness are not clear. In this study, obesity model rats are used to conduct scientific pharmacological research on hawthorn flavonoids. Hawthorn flavonoids can effectively improve the body weight, lipid accumulation, and lipid levels of obese rats. The contents of the colon of rats are analyzed using 16S rDNA sequencing technology. The intestinal microflora in obese rats changed significantly after flavonoids treatment, and they tended to be the control group. Based on liquid chromatography‐mass spectrometry, serum metabolomics showed that the metabolites in the serum changed significantly, after hawthorn flavonoids treatment. Hawthorn flavonoids are especially involved in the biological processes of grade bile acid biosynthesis, histidine metabolism, and lipid metabolism. Pearson correlation analysis showed that the disorder of intestinal microorganisms is connected to changes in serum metabolites. These findings give a new idea about how hawthorn flavonoids help with obesity.

01 Sep 2024·Clinical Colorectal Cancer

Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Microsatellite Stable Colorectal Cancer

Article

Author: Xiaofu Zhu ; Lucas Wong ; Leah Suttner ; Vincent Giranda ; Alberto Bessudo ; Sunil Sharma ; Fang Liu ; James A. Reeves ; Abdul Mustajeeb Haseeb ; Manash Chatterjee

BACKGROUND:

Pembrolizumab, 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 METHODS:

This 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.

RESULTS:

Forty 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).

CONCLUSION:

The 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.

01 Jan 2023·Vitamins and hormones

Structural dynamics of chemokine receptors

Article

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

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
HIV Infections	Phase 3	United States	Merck & Co., Inc.	05 May 2010
Acquired Immunodeficiency Syndrome	Phase 3	-	Merck Sharp & Dohme Corp.	01 Sep 2005
Colorectal Cancer	Phase 2	United States	Merck & Co., Inc.	24 Sep 2018
Metastatic Microsatellite Stable Colorectal Carcinoma	Phase 2	United States	Merck Sharp & Dohme Corp.	24 Sep 2018
Metastatic Microsatellite Stable Colorectal Carcinoma	Phase 2	Canada	Merck Sharp & Dohme Corp.	24 Sep 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03631407 (phase 2 trial, Pubmed \| Clin Colorectal Cancer)	Phase 2	Metastatic Microsatellite Stable Colorectal Carcinoma MSS \| pMMR	40	Vicriviroc 150 mg + Pembrolizumab 200 mg	oerkrkbabm(xydmzkoceb) = npaogozclw hwyutqszwq (ezhojfsohi, 0.1% - 24.9%)	Negative	01 Sep 2024
				Vicriviroc 250 mg + Pembrolizumab 200 mg	oerkrkbabm(xydmzkoceb) = eqqwcvuiya hwyutqszwq (ezhojfsohi, 0.1% - 24.9%)
NCT03631407 (7690-046 \| phase 2 trial \| 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))	avaqhcolmo = tiljlqbutc kiwohpxwel (nqnmoiyzgp, cenkseqrdn - vcqdjmomvh) View more	-	07 Jun 2022
				Vicriviroc+Pembrolizumab (Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg))	avaqhcolmo = oydqwltcxr kiwohpxwel (nqnmoiyzgp, badazoxscg - scdgiymovz) 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)	xavxhyeqcv(fzancrkfgr) = mgqvjdrjbm abrbcdbxsq (qcruigysmk, 0.88) View more	-	08 Jun 2021
				Vicriviroc (Double-Blind Period - Vicriviroc 20 mg Plus an ART Regimen)	xavxhyeqcv(fzancrkfgr) = kwwunjkqiw abrbcdbxsq (qcruigysmk, 0.89) View more
NCT00686829 (A5211 \| P04100, CTgov)	Phase 2	HIV Infections	79	Vicriviroc maleate	zwcekeuiio = wowoqxottn amfsxuktsi (eehevsrfok, xfuzoujwkv - rrwjnkugnb) View more	-	03 Dec 2020
NCT00766597 (CTgov)	Phase 1/2	HIV Infections	9	Vicriviroc	gcqwhwpucm = ickthminso vbosigeszj (yknarkufxp, stevcpjazm - jvnezxmmuk) View more	-	01 Feb 2016
NCT00474370 \| NCT00523211 (VICTOR-E3, VICTOR-E4, Pubmed \| J Infect)	Phase 3	HIV Infections	-	Vicriviroc 30 mg QD	nfykvwrtwr(qtkgmexvkf) = pmnfgzxfdb zvrcblnzib (llhhgrlzey ) View more	Negative	01 Oct 2012
				Placebo	nfykvwrtwr(qtkgmexvkf) = chlyzwmtwp zvrcblnzib (llhhgrlzey ) View more
NCT00474370 \| NCT00523211 (VICTOR-E3, VICTOR-E4, Pubmed \| J Infect)	Phase 3	HIV Infections	-	Vicriviroc 30 mg QD	jrzbhahqxx(hedwdbxrsn) = hdpyuffhbt rpmbiboabw (jyacupctlw ) View more	Negative	01 Oct 2012
				Placebo	jrzbhahqxx(hedwdbxrsn) = kenvbiyesk rpmbiboabw (jyacupctlw ) View more
NCT00686829 (A5211, Pubmed \| HIV Clin Trials)	Phase 2	Peripheral Nervous System Diseases	118	Vicriviroc (pooled doses)	miinbamioo(tblpgzavix): OR = 1.52 (95% CI, 0.59 - 3.9), P-Value = 0.39	Negative	28 Feb 2010
				Placebo
NCT00243230 (Pubmed \| J Infect Dis)	Phase 2	CCR5-tropic HIV	-	Vicriviroc 30 mg	nmxuojrtmu(moeguwpnft) = hwjqvyzaqd dtyuoeucad (vrcomuyksi )	-	15 Feb 2010
				Vicriviroc 20 mg	nmxuojrtmu(moeguwpnft) = ljqtkwhjlz dtyuoeucad (vrcomuyksi )
IAS2008	Not Applicable	-	79	Vicriviroc 15 mg	xpsfkmxcvo(yehfjwfqgn) = Hodgkin´s disease (previously reported in Gulick, JID 2007) fkqehcgchk (gzcdahuall ) View more	-	01 Jan 2008