VICRIVIROC MALEATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H38F3N5O2.C4H4O4
Molecular Weight	649.701
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.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=GXINKQQWHLIBJA-UCIBKFKQSA-N

InChI=1S/C28H38F3N5O2.C4H4O4/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;5-3(6)1-2-4(7)8/h6-9,18-19,24H,10-17H2,1-5H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/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
Anti-HIV agents. Vicriviroc: is the risk of cancer increased?	2006 Aug-Sep	17209230
Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1.	2006 Oct	17005807
New targets in antiretroviral therapy 2006.	2006 Sep	19372844
Recent advances of CCR5 antagonists.	2006 Sep	19372835
Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a fitness loss.	2007 Jun	17542646
Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults.	2007 Jun 19	17545705
Maraviroc: the evidence for its potential in the management of HIV.	2007 Mar 31	21221194
HIV-1 drug-resistance and drug-dependence.	2007 Oct 25	17961213
New approaches in the treatment of HIV/AIDS - focus on maraviroc and other CCR5 antagonists.	2008 Apr	18728830
Long-term safety study of vicriviroc presented.	2008 Dec	19227564
Better results from vicriviroc with new Trofile test.	2008 Dec	19227563
Topical application of entry inhibitors as "virustats" to prevent sexual transmission of HIV infection.	2008 Dec 18	19094217
Scaling up programmatic management of drug-resistant tuberculosis: a prioritized research agenda.	2008 Jul 8	18613746
Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists.	2008 Mar	18096812
Phase II study of vicriviroc versus efavirenz (both with zidovudine/lamivudine) in treatment-naive subjects with HIV-1 infection.	2008 Oct 15	18783318
[Chemokine receptors and its importance in the replication cycle of human immunodeficiency virus: clinical and therapeutic implications].	2008 Sep-Oct	19187693
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
Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry.	2009 Aug	19680536
Pharmacotherapy of pediatric and adolescent HIV infection.	2009 Jun	19707256
The fusion inhibitor enfuvirtide in recent antiretroviral strategies.	2009 Mar	19339955
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
Pharmacokinetics and drug-drug interactions of antiretrovirals: an update.	2010 Jan	19665485
Vicriviroc and peripheral neuropathy: results from AIDS Clinical Trials Group 5211.	2010 Jan-Feb	20400411
Disappointing results for vicriviroc.	2010 Mar	20238442
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
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
Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance.	2012 Jul 5	22520838

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 MALEATE

Official Name

English

SCH 417690

Code

English

SCH-417690

Code

English

VICRIVIROC MALEATE [MI]

Common Name

English

VICRIVIROC MALEATE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1660