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

Molecular Formula	C28H38F3N5O2
Molecular Weight	533.6288
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

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
Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-[2-methoxy-1(R)-4-(trifluoromethyl)phenyl]ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a potent, highly selective, and orally bioavailable CCR5 antagonist.	2004 May 6	15115380
CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection.	2005	16329283
Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1.	2005 Dec	16304152
New targets in antiretroviral therapy 2006.	2006 Sep	19372844
Identification of human liver cytochrome P450 enzymes involved in biotransformation of vicriviroc, a CCR5 receptor antagonist.	2007 Dec	17827338
HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211.	2007 Feb 15	17243065
Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a fitness loss.	2007 Jun	17542646
Maraviroc: the evidence for its potential in the management of HIV.	2007 Mar 31	21221194
Access denied? The status of co-receptor inhibition to counter HIV entry.	2007 May	17472538
CCR5 antagonists in the treatment of treatment-experienced patients infected with CCR5 tropic HIV-1.	2007 Oct 15	17933723
CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature.	2007 Oct 15	17933722
Mapping resistance to the CCR5 co-receptor antagonist vicriviroc using heterologous chimeric HIV-1 envelope genes reveals key determinants in the C2-V5 domain of gp120.	2008 Apr 10	18190945
Long-term safety study of vicriviroc presented.	2008 Dec	19227564
Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice.	2008 Dec 5	18809675
Scaling up programmatic management of drug-resistant tuberculosis: a prioritized research agenda.	2008 Jul 8	18613746
[CCR5 antagonists: a new class of antiretrovirals].	2008 Mar	18455055
Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists.	2008 Mar	18096812
Distinct efficacy of HIV-1 entry inhibitors to prevent cell-to-cell transfer of R5 and X4 viruses across a human placental trophoblast barrier in a reconstitution model in vitro.	2008 Mar 31	18377645
Drug interactions with new and investigational antiretrovirals.	2009	19492868
Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry.	2009 Aug	19680536
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
CCR5 inhibitors: Emerging promising HIV therapeutic strategy.	2009 Jan	21938106
Gateways to clinical trials.	2009 Jul-Aug	19798455
Novel drug classes: entry inhibitors [enfuvirtide, chemokine (C-C motif) receptor 5 antagonists].	2009 Nov	20048719
Efavirenz: a decade of clinical experience in the treatment of HIV.	2009 Nov	19767318
Gateways to clinical trials.	2010 Dec	21225012
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
Gateways to clinical trials.	2010 Jun	20664824
HIV-1 Entry, Inhibitors, and Resistance.	2010 May	21994672
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
GenHtr: a tool for comparative assessment of genetic heterogeneity in microbial genomes generated by massive short-read sequencing.	2010 Oct 12	20939910
Conjugation of cell-penetrating peptides leads to identification of anti-HIV peptides from matrix proteins.	2012 Feb 15	22277590

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:48:50 GMT 2023` Edited by `admin` on `Fri Dec 15 15:48:50 GMT 2023`
Record UNII	EP3QG127N9
Record Status	`Validated (UNII)`
Record Version

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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