Target Information

Target General Information

Target ID

T09960 (Former ID: TTDS00326)

Target Name

C-C chemokine receptor type 5 (CCR5)

Synonyms

HIV-1 fusion coreceptor; HIV-1 fusion co-receptor; Chemokine receptor CCR5; CMKBR5; CHEMR13; CD195 antigen; CD195; CCR-5; CC-CKR-5; C-C CKR-5

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Gene Name

CCR5

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Human immunodeficiency virus disease [ICD-11: 1C60-1C62]

Function

May play a role in the control of granulocytic lineage proliferation or differentiation. Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level.

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BioChemical Class

GPCR rhodopsin

UniProt ID

CCR5_HUMAN

Sequence

MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T02OOS

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Maraviroc

Drug Info

Approved

Human immunodeficiency virus infection

[2], [3], [4]

Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

E-913

Drug Info

Phase 3

Human immunodeficiency virus infection

[5], [6]

PRO-140

Drug Info

Phase 3

Human immunodeficiency virus infection

[7]

Vicriviroc

Drug Info

Phase 3

Human immunodeficiency virus infection

[8], [9]

BMS-813160

Drug Info

Phase 2

Diabetic nephropathy

[15]

PF-232798

Drug Info

Phase 2

Human immunodeficiency virus infection

[16]

SB-728-T

Drug Info

Phase 2

Human immunodeficiency virus infection

[7]

Cal-1

Drug Info

Phase 1/2

Human immunodeficiency virus-1 infection

[17]

CCR5 mab

Drug Info

Phase 1

Human immunodeficiency virus infection

[18]

INCB15050

Drug Info

Phase 1

Human immunodeficiency virus infection

[19]

Tak-220

Drug Info

Phase 1

Human immunodeficiency virus-1 infection

[20], [21]

VCH-286

Drug Info

Phase 1

Human immunodeficiency virus infection

[22]

Discontinued Drug(s)

[+] 5 Discontinued Drugs

GW873140

Drug Info

Discontinued in Phase 3

Human immunodeficiency virus-1 infection

[23], [24]

AZD8566

Drug Info

Discontinued in Phase 1

Rheumatoid arthritis

[25]

SCH-C

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[26], [27]

AZD5672

Drug Info

Terminated

Rheumatoid arthritis

[30], [31]

CCR5Qb

Drug Info

Terminated

Human immunodeficiency virus infection

[32]

Mode of Action

[+] 4 Modes of Action

Antagonist

[+] 9 Antagonist drugs

Maraviroc

Drug Info

[1], [33], [34]

E-913

Drug Info

[35]

PRO-140

Drug Info

[36]

Vicriviroc

Drug Info

[37]

PF-232798

Drug Info

[16]

INCB15050

Drug Info

[42]

VCH-286

Drug Info

[22]

AZD8566

Drug Info

[45]

AZD5672

Drug Info

[45]

Modulator

[+] 4 Modulator drugs

BMS-813160

Drug Info

[38], [39]

SB-728-T

Drug Info

[40]

Cal-1

Drug Info

[41]

NIFEVIROC

Drug Info

[52]

Binder

[+] 3 Binder drugs

Tak-220

Drug Info

[43]

GW873140

Drug Info

[44], [43]

SCH-C

Drug Info

[43]

Inhibitor

[+] 8 Inhibitor drugs

(2-(4-chlorobenzyloxy)-5-bromophenyl)methanamine

Drug Info

[47]

4-(2-(4-chlorobenzyloxy)-5-bromobenzyl)morpholine

Drug Info

[48]

ANIBAMINE

Drug Info

[49]

CMPD-167

Drug Info

[50]

GT-1282

Drug Info

[51]

N-(2-(4-chlorobenzyloxy)-5-bromobenzyl)ethanamine

Drug Info

[47]

SCH-210971

Drug Info

[53]

VARIECOLIN

Drug Info

[54]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Maraviroc

Ligand Info

Structure Description

Crystal Structure of the CCR5 Chemokine Receptor

PDB:4MBS

Method

X-ray diffraction

Resolution

2.71 Å

Mutation

Yes

[55]

PDB Sequence

PCQKINVKQI

²⁸

AARLLPPLYS

³⁸

LVFIFGFVGN

⁴⁸

MLVILILINY

⁵⁸

KRLKSMTDIY

⁶⁸

LLNLAISDLF

⁷⁸

FLLTVPFWAH

⁸⁸

YAAAQWDFGN

⁹⁸

TMCQLLTGLY

¹⁰⁸

FIGFFSGIFF

¹¹⁸

IILLTIDRYL

¹²⁸

AVVHAVFALK

¹³⁸

ARTVTFGVVT

¹⁴⁸

SVITWVVAVF

¹⁵⁸

ASLPNIIFTR

¹⁶⁸

SQKEGLHYTC

¹⁷⁸

SSHFPYSQYQ

¹⁸⁸

FWKNFQTLKI

¹⁹⁸

VILGLVLPLL

²⁰⁸

VMVICYSGIL

²¹⁸

KTLLRMKKYT

¹⁰⁰⁵

CTVCGYIYNP

¹⁰¹⁵

EDGDPDNGVN

¹⁰²⁵

PGTDFKDIPD

¹⁰³⁵

DWVCPLCGVG

¹⁰⁴⁵

KDQFEEVEEE

²²⁷

KKRHRDVRLI

²³⁷

FTIMIVYFLF

²⁴⁷

WAPYNIVLLL

²⁵⁷

NTFQEFFGLN

²⁶⁷

NCSSSNRLDQ

²⁷⁷

AMQVTETLGM

²⁸⁷

THCCINPIIY

²⁹⁷

AFVGEEFRNY

³⁰⁷

LLVFFQ

Residue

Distance (Å)

TYR37

3.106

TRP86

3.510

TYR89

3.642

THR105

4.641

TYR108

3.619

PHE109

3.482

PHE112

3.714

PHE182

3.206

LYS191

3.757

GLN194

3.837

THR195

3.291

Residue

Distance (Å)

ILE198

3.765

TRP248

3.655

TYR251

3.019

LEU255

3.718

THR259

3.416

MET279

3.869

GLN280

4.913

GLU283

2.799

THR284

3.719

MET287

3.934

Ligand Name: Oleic acid

Ligand Info

Structure Description

Crystal Structure of CC Chemokine Receptor 5 (CCR5) in complex with high potency HIV entry inhibitor 5P7-CCL5

PDB:5UIW

Method

X-ray diffraction

Resolution

2.20 Å

Mutation

Yes

[56]

PDB Sequence

TSEPCQKINV

²⁵

KQIAARLLPP

³⁵

LYSLVFIFGF

⁴⁵

VGNMLVILIL

⁵⁵

INYKRLKSMT

⁶⁵

DIYLLNLAIS

⁷⁵

DLFFLLTVPF

⁸⁵

WAHYAAAQWD

⁹⁵

FGNTMCQLLT

¹⁰⁵

GLYFIGFFSG

¹¹⁵

IFFIILLTID

¹²⁵

RYLAVVHAVF

¹³⁵

ALKARTVTFG

¹⁴⁵

VVTSVITWVV

¹⁵⁵

AVFASLPNII

¹⁶⁵

FTRSQKEGLH

¹⁷⁵

YTCSSHFPYS

¹⁸⁵

QYQFWKNFQT

¹⁹⁵

LKIVILGLVL

²⁰⁵

PLLVMVICYS

²¹⁵

GILKTLLRMK

¹⁰⁰²

KYTCTVCGYI

¹⁰¹²

YNPEDGDPDN

¹⁰²²

GVNPGTDFKD

¹⁰³²

IPDDWVCPLC

¹⁰⁴²

GVGKDQFEEV

¹⁰⁵²

EEEKKRHRDV

²³⁴

RLIFTIMIVY

²⁴⁴

FLFWAPYNIV

²⁵⁴

LLLNTFQEFF

²⁶⁴

GLNNCSSSNR

²⁷⁴

LDQAMQVTET

²⁸⁴

LGMTHCCINP

²⁹⁴

IIYAFVGEEF

³⁰⁴

RNYLLVFFQK

³¹⁴

Residue

Distance (Å)

ARG235

3.335

THR239

3.981

ILE242

3.207

VAL243

4.092

LEU246

3.771

PHE247

4.370

Residue

Distance (Å)

ILE292

3.883

ILE295

4.697

ILE296

4.792

PHE299

4.629

VAL300

4.189

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Olfactory receptor 10A5 (OR10A5)	PF13853	25.166 (76/302)	3.08E-06
Olfactory receptor 2Z1 (OR2Z1)	PF13853	23.673 (58/245)	3.75E-06
Olfactory receptor 6S1 (OR6S1)	PF13853	23.729 (70/295)	7.96E-05
Olfactory receptor 10A2 (OR10A2)	PF13853	24.834 (75/302)	9.73E-05
Olfactory receptor 10G8 (OR10G8)	PF13853	22.353 (57/255)	1.17E-04
Olfactory receptor 10G7 (OR10G7)	PF13853	23.950 (57/238)	2.41E-04
Olfactory receptor 10G9 (OR10G9)	PF13853	23.529 (56/238)	2.59E-04
Olfactory receptor 2A1/2A42 (OR2A1; OR2A42)	PF13853	24.348 (56/230)	2.73E-04
Olfactory receptor 10W1 (OR10W1)	PF13853	25.238 (53/210)	4.98E-04
Olfactory receptor 1E1 (OR1E1)	PF13853	22.526 (66/293)	1.00E-03
Olfactory receptor 4K2 (OR4K2)	PF13853	22.807 (52/228)	1.00E-03
Olfactory receptor 1D2 (OR1D2)	PF13853	22.483 (67/298)	1.00E-03
Olfactory receptor 2T3 (OR2T3)	PF13853	21.356 (63/295)	2.00E-03
Olfactory receptor 13C4 (OR13C4)	PF13853	28.155 (29/103)	3.00E-03
Olfactory receptor 2T34 (OR2T34)	PF13853	21.356 (63/295)	3.00E-03
Olfactory receptor 2A5 (OR2A5)	PF13853	24.091 (53/220)	3.00E-03
Olfactory receptor 2A4 (OR2A4)	PF13853	24.561 (56/228)	4.00E-03
Olfactory receptor 51E2 (OR51E2)	PF13853	26.316 (80/304)	5.00E-03
Click to Show/Hide the Information of Human Similarity Proteins

KEGG Pathway	Pathway ID	Affiliated Target
Viral life cycle - HIV-1	hsa03250	Affiliated Target
Class: Genetic Information Processing => Information processing in viruses	Pathway Hierarchy
Virion - Human immunodeficiency virus	hsa03260	Affiliated Target
Class: Genetic Information Processing => Information processing in viruses	Pathway Hierarchy
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Viral protein interaction with cytokine and cytokine receptor	hsa04061	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Chemokine signaling pathway	hsa04062	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Endocytosis	hsa04144	Affiliated Target
Class: Cellular Processes => Transport and catabolism	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	17	Degree centrality	1.83E-03	Betweenness centrality	6.23E-04
Closeness centrality	2.15E-01	Radiality	1.38E+01	Clustering coefficient	1.54E-01
Neighborhood connectivity	2.11E+01	Topological coefficient	1.00E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 5 KEGG Pathways

Cytokine-cytokine receptor interaction

Chemokine signaling pathway

Endocytosis

Toxoplasmosis

Viral carcinogenesis

NetPath Pathway

[+] 3 NetPath Pathways

TSLP Signaling Pathway

TCR Signaling Pathway

IL2 Signaling Pathway

Panther Pathway

[+] 1 Panther Pathways

Inflammation mediated by chemokine and cytokine signaling pathway

PID Pathway

[+] 1 PID Pathways

IL12-mediated signaling events

Reactome

[+] 3 Reactome Pathways

Binding and entry of HIV virion

Chemokine receptors bind chemokines

G alpha (i) signalling events

WikiPathways

[+] 7 WikiPathways

TCR Signaling Pathway

GPCRs, Class A Rhodopsin-like

HIV Life Cycle

Peptide GPCRs

GPCR ligand binding

GPCR downstream signaling

GPCRs, Other

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

Rapamycin enhances aplaviroc anti-HIV activity: implications for the clinical development of novel CCR5 antagonists. Antiviral Res. 2009 Jul;83(1):86-9.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 806).

REF 3

2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.

REF 4

Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.

REF 5

REF 6

ClinicalTrials.gov (NCT00297076) Chemokine Coreceptor 5 (CCR5) Antagonist GW873140 In R5-Tropic Treatment-Experienced HIV-Infected Subjects. U.S. National Institutes of Health.

REF 7

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 8

REF 9

Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.

REF 10

ClinicalTrials.gov (NCT03902522) PRO 140 in Treatment-Experienced HIV-1 Subjects. U.S. National Institutes of Health.

REF 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023697)

REF 12

ClinicalTrials.gov (NCT00979771) A Study to Investigate the Ability of GSK706769 to Maintain Clinical Remission After Withdrawal of Enbrel in Rheumatoid Arthritis Patients. U.S. National Institutes of Health.

REF 13

REF 14

The dual CCR5 and CCR2 inhibitor cenicriviroc does not redistribute HIV into extracellular space: implications for plasma viral load and intracellular DNA decline. J Antimicrob Chemother. 2015 Mar;70(3):750-6.

REF 15

ClinicalTrials.gov (NCT01752985) Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease. U.S. National Institutes of Health.

REF 16

An imidazopiperidine series of CCR5 antagonists for the treatment of HIV: the discovery of N-{(1S)-1-(3-fluorophenyl)-3-[(3-endo)-3-(5-isobutyryl-2-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]propyl}acetamide (PF-232798). J Med Chem. 2011 Jan 13;54(1):67-77.

REF 17

ClinicalTrials.gov (NCT01734850) Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-1 Infection. U.S. National Institutes of Health.

REF 18

CCR5 Monoclonal Antibodies for HIV-1 Therapy. Curr Opin HIV AIDS. 2009 March; 4(2): 104-111.

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025519)

REF 20

REF 21

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022281)

REF 22

The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets. Mol Biol Int. 2012;2012:401965.

REF 23

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018317)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027710)

REF 26

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014207)

REF 28

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012061)

REF 30

REF 31

Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate. Arthritis Rheum. 2010 Nov;62(11):3154-60.

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021743)

REF 33

Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell. 1999 Mar 5;96(5):667-76.

REF 34

Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996 Mar 19;35(11):3362-7.

REF 35

Species selectivity of small-molecular antagonists for the CCR5 chemokine receptor. Int Immunopharmacol. 2007 Dec 5;7(12):1528-34.

REF 36

Agonist-induced internalization of CC chemokine receptor 5 as a mechanism to inhibit HIV replication. J Pharmacol Exp Ther. 2011 Jun;337(3):655-62.

REF 37

HIV entry: new insights and implications for patient management. Curr Opin Infect Dis. 2009 Feb;22(1):35-42.

REF 38

A dual CCR2/CCR5 chemokine antagonist, BMS-813160. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.

REF 39

Methods for improving thymic recovery and preventing and treating graft versus host disease using ccr2 and ccr5 antagonists

REF 40

Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV. N Engl J Med. 2014 March 6; 370(10): 901-910.

REF 41

Preclinical safety and efficacy of an anti-HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor. Mol Ther Methods Clin Dev. 2014 Feb 12;1:11.

REF 42

Incyte. Product Development Pipeline.

REF 43

Progress in targeting HIV-1 entry. Drug Discov Today. 2005 Aug 15;10(16):1085-94.

REF 44

In vitro and clinical investigation of the relationship between CCR5 receptor occupancy and anti-HIV activity of Aplaviroc. J Clin Pharmacol. 2008 Oct;48(10):1179-88.

REF 45

Clinical pipeline report, company report or official report of AstraZeneca (2009).

REF 46

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021743)

REF 47

CCR5 receptor antagonists: discovery and SAR of novel 4-hydroxypiperidine derivatives. Bioorg Med Chem Lett. 2007 Apr 1;17(7):1883-7.

REF 48

CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives. Bioorg Med Chem Lett. 2007 Jan 1;17(1):231-4.

REF 49

Isolation and structure of antagonists of chemokine receptor (CCR5). J Nat Prod. 2004 Jun;67(6):1036-8.

REF 50

REF 51

Reduced cardiac side-effect potential by introduction of polar groups: discovery of NIBR-1282, an orally bioavailable CCR5 antagonist which is acti... Bioorg Med Chem Lett. 2008 Mar 15;18(6):2000-5.

REF 52

Determination of nifeviroc, a novel CCR5 antagonist: application to a pharmacokinetic study. J Pharm Biomed Anal. 2011 Nov 1;56(3):637-40.

REF 53

Chemokine receptor CCR-5 inhibitors produced by Chaetomium globosum. J Nat Prod. 2006 Jul;69(7):1025-8.

REF 54

Inhibition of the human chemokine receptor CCR5 by variecolin and variecolol and isolation of four new variecolin analogues, emericolins A-D, from ... J Nat Prod. 2004 Oct;67(10):1681-4.

REF 55

Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex. Science. 2013 Sep 20;341(6152):1387-90.

REF 56

Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist Reveals Mechanisms of Chemokine Recognition and Molecular Mimicry by HIV. Immunity. 2017 Jun 20;46(6):1005-1017.e5.

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