VICRIVIROC

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H38F3N5O2
Molecular Weight	533.6288
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC[C@H](N1CCN(C[C@@H]1C)C2(C)CCN(CC2)C(=O)C3=C(C)N=CN=C3C)C4=CC=C(C=C4)C(F)(F)F

InChI

InChIKey=CNPVJJQCETWNEU-CYFREDJKSA-N

InChI=1S/C28H38F3N5O2/c1-19-16-35(14-15-36(19)24(17-38-5)22-6-8-23(9-7-22)28(29,30)31)27(4)10-12-34(13-11-27)26(37)25-20(2)32-18-33-21(25)3/h6-9,18-19,24H,10-17H2,1-5H3/t19-,24-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26991320 | https://www.poz.com/article/hiv-vicriviroc-merck-18742-4657
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16304152 | https://aidsinfo.nih.gov/drugs/519/vicriviroc/0/patient

Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. vicriviroc binds specifically to the CCR5 receptor and prevents infection of target cells by CCR5-tropic HIV-1 isolates. In antiviral assays, vicriviroc showed potent, broad-spectrum activity against genetically diverse and drug-resistant HIV-1 isolates and was consistently more active than SCH-C in inhibiting viral replication. This compound demonstrated synergistic anti-HIV activity in combination with drugs from all other classes of approved antiretrovirals. Competition binding assays revealed that vicriviroc binds with higher affinity to CCR5 than SCH-C. Functional assays, including inhibition of calcium flux, guanosine 5'-[35S]triphosphate exchange, and chemotaxis, confirmed that vicriviroc acts as a receptor antagonist by inhibiting signaling of CCR5 by chemokines. Finally, vicriviroc demonstrated diminished affinity for the human ether a-go-go related gene transcript ion channel compared to SCH-C, suggesting a reduced potential for cardiac effects. Vicriviroc represented a promising new candidate for the treatment of HIV-1 infection. Vicriviroc for HIV treatment was previously in Phase III studies but has since been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
C-C chemokine receptor type 5 19 Target ID: CHEMBL274 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16304152 \| https://www.ncbi.nlm.nih.gov/pubmed/22931505	Antagonist 2778		0.8 nM [Ki]
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16304152	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22637726	Primary		Preclinical	Unknown Approved Use Unknown
HIV-1 infection 151 Sources: http://adisinsight.springer.com/drugs/800017158 https://clinicaltrials.gov/ct2/show/NCT00474370	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
63 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
131 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
181 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999	15 mg 1 times / day steady-state, oral dose: 15 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
149 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	20.5 mg 2 times / day steady-state, oral dose: 20.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
342 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	41.1 mg 2 times / day steady-state, oral dose: 41.1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
65 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	8.2 mg 2 times / day steady-state, oral dose: 8.2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1172 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2502 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3390 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20071999	15 mg 1 times / day steady-state, oral dose: 15 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1060 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	20.5 mg 2 times / day steady-state, oral dose: 20.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2290 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	41.1 mg 2 times / day steady-state, oral dose: 41.1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
424 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	8.2 mg 2 times / day steady-state, oral dose: 8.2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
29 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	20.5 mg 2 times / day steady-state, oral dose: 20.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	41.1 mg 2 times / day steady-state, oral dose: 41.1 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17545705	8.2 mg 2 times / day steady-state, oral dose: 8.2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VICRIVIROC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00E9SW	https://www.1pchem.com/search?query=1P00E9SW
AK Scientific	X5032	https://aksci.com/item_detail.php?cat=X5032
AK Scientific	X7271	https://aksci.com/item_detail.php?cat=X7271
ApexBio Technology	A2589	https://www.apexbt.com/catalogsearch/result/?q=A2589
ApexBio Technology	A3916	https://www.apexbt.com/catalogsearch/result/?q=A3916
AstaTech	40677	http://astatechinc.com/CPSResult.php?CRNO=40677
BLD Pharm	BD156419	http://www.bldpharm.com/search/Search.html?keyword=BD156419
BOC Sciences	599179-03-0	http://www.bocsci.com/description.asp?cas=599179-03-0
Chem Scene	CS-1019	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1019
ChemShuttle	157188	https://www.chemshuttle.com/catalogsearch/result/?q=157188
ChemShuttle	169497	https://www.chemshuttle.com/catalogsearch/result/?q=169497
Debye Scientific	DA-42140	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-42140
Excenen	EX-A199	http://www.excenen.com/searchresultlist.php?id=EX-A199
Fluorochem	80288	http://www.fluorochem.co.uk/Products/Product?code=080288
MedChem Express	HY-17377	https://www.medchemexpress.com/search.html?q=HY-17377&ft=&fa=&fp=
MolPort	MolPort-005-933-298	https://www.molport.com/shop/molecule-link/MolPort-005-933-298
MolPort	MolPort-016-633-267	https://www.molport.com/shop/molecule-link/MolPort-016-633-267
Molnova	M15229	https://www.molnova.com/en/serch-list.html?keywords=M15229
MuseChem	I010027	https://www.musechem.com/product/I010027.html
MuseChem	I011701	https://www.musechem.com/product/I011701.html
ShangHai Biochempartner	BCP000150	http://www.biochempartner.com/search_BCP000150
ShangHai Biochempartner	BCP01856	http://www.biochempartner.com/search_BCP01856
TargetMol	T3435	https://www.targetmol.com/search?keyword=T3435
eMolecules	110041682	https://orderbb.emolecules.com/search/#?query=110041682
eMolecules	43639407	https://orderbb.emolecules.com/search/#?query=43639407
eMolecules	44786351	https://orderbb.emolecules.com/search/#?query=44786351
eMolecules	45475415	https://orderbb.emolecules.com/search/#?query=45475415
eMolecules	85163669	https://orderbb.emolecules.com/search/#?query=85163669
eNovation Chemicals	D501746	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501746&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-2241135614	https://mcule.com/MCULE-2241135614/
mcule	MCULE-3959045859	https://mcule.com/MCULE-3959045859/
mcule	MCULE-5245707731	https://mcule.com/MCULE-5245707731/
mcule	MCULE-5656172405	https://mcule.com/MCULE-5656172405/
mcule	MCULE-5727399555	https://mcule.com/MCULE-5727399555/

PubMed

Title	Date	PubMed
New targets in antiretroviral therapy 2006.	2006 Sep	19372844
Recent advances of CCR5 antagonists.	2006 Sep	19372835
Maraviroc: the evidence for its potential in the management of HIV.	2007 Mar 31	21221194
Long-term safety study of vicriviroc presented.	2008 Dec	19227564
Better results from vicriviroc with new Trofile test.	2008 Dec	19227563
Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy.	2009	22096378
Drug interactions with new and investigational antiretrovirals.	2009	19492868
Novel compounds for the treatment of HIV type-1 infection.	2009	19483267
The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapies.	2009 Apr	19250135
Antiretroviral therapy: new drugs, formulations, ideas, and strategies.	2009 Dec	20068261
Response to vicriviroc in treatment-experienced subjects, as determined by an enhanced-sensitivity coreceptor tropism assay: reanalysis of AIDS clinical trials group A5211.	2009 Dec 1	19874179
Maraviroc in the treatment of HIV infection.	2009 Feb 6	19920903
CCR5 inhibitors: Emerging promising HIV therapeutic strategy.	2009 Jan	21938106
Gateways to clinical trials.	2009 Jul-Aug	19798455
Pharmacotherapy of pediatric and adolescent HIV infection.	2009 Jun	19707256
The fusion inhibitor enfuvirtide in recent antiretroviral strategies.	2009 Mar	19339955
A pièce de resistance: how HIV-1 escapes small molecule CCR5 inhibitors.	2009 Mar	19339950
HIV-1 entry inhibitors: an overview.	2009 Mar	19339945
Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities.	2009 May 10	19303620
Novel drug classes: entry inhibitors [enfuvirtide, chemokine (C-C motif) receptor 5 antagonists].	2009 Nov	20048719
Long-term data on vicriviroc released.	2009 Nov	19938348
Profile of maraviroc: a CCR5 antagonist in the management of treatment-experienced HIV patients.	2010	22096393
Pharmacokinetic/pharmacodynamic modeling of the antiretroviral activity of the CCR5 antagonist Vicriviroc in treatment experienced HIV-infected subjects (ACTG protocol 5211).	2010 Apr	20071999
Clinical resistance to vicriviroc through adaptive V3 loop mutations in HIV-1 subtype D gp120 that alter interactions with the N-terminus and ECL2 of CCR5.	2010 Apr 25	20172579
Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients.	2010 Aug	20672447
Gateways to clinical trials.	2010 Dec	21225012
Potential use of rapamycin in HIV infection.	2010 Dec	21175433
Evolution of CCR5 antagonist resistance in an HIV-1 subtype C clinical isolate.	2010 Dec	20856130
C-C chemokine receptor type 5 (CCR5) utilization of transmitted and early founder human immunodeficiency virus type 1 envelopes and sensitivity to small-molecule CCR5 inhibitors.	2010 Dec	20810746
Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution.	2010 Dec 14	21156072
CCR5: From Natural Resistance to a New Anti-HIV Strategy.	2010 Feb	21994649
Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial.	2010 Feb 15	20064072
Short-term administration of the CCR5 antagonist vicriviroc to patients with HIV and HCV coinfection is safe and tolerable.	2010 Jan	19838130
Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211.	2010 Jan-Feb	20400411
Short communication: antiretroviral therapy resistance mutations present in the HIV type 1 subtype C pol and env regions from therapy-naive patients in Zambia.	2010 Jul	20623996
Gateways to clinical trials.	2010 Jun	20664824
Renal insufficiency has no effect on the pharmacokinetics of vicriviroc in a ritonavir-containing regimen.	2010 Jun	20481650
Disappointing results for vicriviroc.	2010 Mar	20238442
HIV-1 Entry, Inhibitors, and Resistance.	2010 May	21994672
Characterization of emergent HIV resistance in treatment-naive subjects enrolled in a vicriviroc phase 2 trial.	2010 May 15	20373959
Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.	2010 Nov 11	21085635
Structure of HIV-1 quasi-species as early indicator for switches of co-receptor tropism.	2010 Nov 30	21118549
A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5.	2010 Oct	20702642
GenHtr: a tool for comparative assessment of genetic heterogeneity in microbial genomes generated by massive short-read sequencing.	2010 Oct 12	20939910
Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV: properties, promises and challenges.	2010 Sep	20712521
Identification and characterization of INCB9471, an allosteric noncompetitive small-molecule antagonist of C-C chemokine receptor 5 with potent inhibitory activity against monocyte migration and HIV-1 infection.	2011 Jul	21459966
Novel 4,4-disubstituted piperidine-based C-C chemokine receptor-5 inhibitors with high potency against human immunodeficiency virus-1 and an improved human ether-a-go-go related gene (hERG) profile.	2011 Jun 9	21539377
Conjugation of cell-penetrating peptides leads to identification of anti-HIV peptides from matrix proteins.	2012 Feb 15	22277590
Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance.	2012 Jul 5	22520838
Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance.	2013 Jun 7	23758814

Patents

Sample Use Guides

In Vivo Use Guide

One tablet of vicriviroc 30 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Vicriviroc potently inhibited all the HIV-1 isolates in PBMCs isolates tested, with geometric mean EC50s ranging between 0.04 nM and 2.3 nM and IC90s between 0.45 nM and 18 nM

Name

Type

Language

VICRIVIROC

Official Name

English

MK-4176

Code

English

SCH-417690 FREE BASE

Code

English

SCH-D

Code

English

MK-7690

Code

English

VICRIVIROC [MI]

Common Name

English

5-((4-((3S)-4-((1R)-2-METHOXY-1-(4-(TRIFLUOROMETHYL)PHENYL)ETHYL)-3-METHYLPIPERAZIN-1-YL)-4-METHYLPIPERIDIN-1-YL)CARBONYL)-4,6-DIMETHYLPYRIMIDINE

Systematic Name

English

vicriviroc [INN]

Common Name

English

Vicriviroc [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C63817