Target Information

Target General Infomation
Target ID
T09960
Former ID
TTDS00326
Target Name
C-C chemokinereceptor type 5
Gene Name
CCR5
Synonyms
C-C CKR-5; CC-CKR-5; CCR-5; CD195 antigen; CHEMR13; Chemokine receptor CCR5; HIV-1 fusion co-receptor; HIV-1 fusion coreceptor; CCR5
Target Type
Successful
Disease Chronic obstructive pulmonary disease; Rheumatoid arthritis [ICD9: 460-519, 490-492, 494-496, 710-719, 714; ICD10: J00-J99, J40-J44, J47, M00-M25, M05-M06]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Diabetic nephropathy [ICD9: 250.4; ICD10: E11.21]
HIV-1 infection [ICD9: 001-139, 042; ICD10: B20-B24]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Infections [ICD9: 001-139; ICD10: A00-B99]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Transplant rejection [ICD9: 279.5, 996; ICD10: D89.8, T86]
Function
Receptor for a c-c type chemokine. Binds to MIP-1-alpha, MIP-1-beta and rantes and subsequently transduces a signal by increasing the intracellular calcium ions level. May play a role in the control of granulocytic lineage proliferation or differentiation.
BioChemical Class
GPCR rhodopsin
Target Validation
T09960
UniProt ID
P51681
Sequence
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
HFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL
Drugs and Mode of Action
Drug(s) Maraviroc Drug Info Approved Human immunodeficiency virus infection [529282], [536223], [542947]
E-913 Drug Info Phase 3 Human immunodeficiency virus infection [521808], [540440]
Maraviroc Drug Info Phase 3 Chronic obstructive pulmonary disease [536223], [542947]
Vicriviroc Drug Info Phase 3 Human immunodeficiency virus infection [536833], [542952]
INCB9471 Drug Info Phase 2a Infections [548244]
BMS-813160 Drug Info Phase 2 Diabetic nephropathy [524165]
Cenicriviroc Drug Info Phase 2 Human immunodeficiency virus infection [533043], [542922]
GSK-706769 Drug Info Phase 2 Human immunodeficiency virus infection [522788]
INCB9471 Drug Info Phase 2 Human immunodeficiency virus infection [549860]
PF-232798 Drug Info Phase 2 Human immunodeficiency virus infection [531280]
PRO-140 Drug Info Phase 2 Human immunodeficiency virus infection [525183]
Cal-1 Drug Info Phase 1/2 HIV-1 infection [524138]
SB-728-T Drug Info Phase 1/2 Human immunodeficiency virus infection [523810]
CCR5 mab Drug Info Phase 1 Human immunodeficiency virus infection [544105]
INCB15050 Drug Info Phase 1 Human immunodeficiency virus infection [548427]
Tak-220 Drug Info Phase 1 HIV-1 infection [542915], [548134]
VCH-286 Drug Info Phase 1 Human immunodeficiency virus infection [531985]
GW873140 Drug Info Discontinued in Phase 3 HIV-1 infection [542944], [547670]
AZD8566 Drug Info Discontinued in Phase 1 Chronic obstructive pulmonary disease; Rheumatoid arthritis [548691]
SCH-C Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [542937], [547223]
AZD5672 Drug Info Terminated Rheumatoid arthritis [531058], [542666]
CCR5 receptor inhibitors Drug Info Terminated Human immunodeficiency virus infection [548211]
CCR5Qb Drug Info Terminated Human immunodeficiency virus infection [548077]
TAK-779 Drug Info Terminated Transplant rejection [542775], [547013]
Inhibitor (2-(4-chlorobenzyloxy)-5-bromophenyl)methanamine Drug Info [528689]
4-(2-(4-chlorobenzyloxy)-5-bromobenzyl)morpholine Drug Info [528511]
ANIBAMINE Drug Info [527121]
CMPD-167 Drug Info [540496]
GT-1282 Drug Info [529307]
N-(2-(4-chlorobenzyloxy)-5-bromobenzyl)ethanamine Drug Info [528689]
SCH-210971 Drug Info [528341]
VARIECOLIN Drug Info [527257]
Antagonist AZD5672 Drug Info [550288]
AZD8566 Drug Info [550288]
CCR5 receptor inhibitors Drug Info [529636]
E-913 Drug Info [536516]
GSK-706769 Drug Info [530181]
INCB15050 Drug Info [551022]
INCB9471 Drug Info [536516]
Maraviroc Drug Info [534846], [537430], [537962]
PF-232798 Drug Info [531280]
PRO-140 Drug Info [531384]
TAK-779 Drug Info [536143], [536516]
VCH-286 Drug Info [531985]
Vicriviroc Drug Info [537478]
Modulator BMS-813160 Drug Info [531630]
Cal-1 Drug Info [533257]
Cenicriviroc Drug Info [533043]
NIFEVIROC Drug Info [531584]
SB-728-T Drug Info [544423]
Binder GW873140 Drug Info [536143], [536797]
SCH-C Drug Info [536143]
Tak-220 Drug Info [536143]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
Chemokine signaling pathway
Endocytosis
Toxoplasmosis
Viral carcinogenesis
NetPath Pathway TSLP Signaling Pathway
TCR Signaling Pathway
IL2 Signaling Pathway
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
Pathway Interaction Database IL12-mediated signaling events
Reactome Binding and entry of HIV virion
Chemokine receptors bind chemokines
G alpha (i) signalling events
WikiPathways TCR Signaling Pathway
GPCRs, Class A Rhodopsin-like
HIV Life Cycle
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
GPCRs, Other
References
Ref 521808ClinicalTrials.gov (NCT00297076) Chemokine Coreceptor 5 (CCR5) Antagonist GW873140 In R5-Tropic Treatment-Experienced HIV-Infected Subjects. U.S. National Institutes of Health.
Ref 522788ClinicalTrials.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 523810ClinicalTrials.gov (NCT01543152) Dose Escalation Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving SB-728-T. U.S. National Institutes of Health.
Ref 524138ClinicalTrials.gov (NCT01734850) Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-1 Infection. U.S. National Institutes of Health.
Ref 524165ClinicalTrials.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 525183ClinicalTrials.gov (NCT02438345) PRO 140 for Human Immunodeficiency Virus. U.S. National Institutes of Health.
Ref 5292822007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
Ref 531058Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate. Arthritis Rheum. 2010 Nov;62(11):3154-60.
Ref 531280An 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 531985The 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 533043The 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 536223Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
Ref 536833Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
Ref 540440(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: 3500).
Ref 542666(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: 7686).
Ref 542775(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: 783).
Ref 542915(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: 800).
Ref 542922(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: 801).
Ref 542937(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: 804).
Ref 542944(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: 805).
Ref 542947(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 542952(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: 807).
Ref 544105CCR5 Monoclonal Antibodies for HIV-1 Therapy. Curr Opin HIV AIDS. 2009 March; 4(2): 104-111.
Ref 547013Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012061)
Ref 547223Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014207)
Ref 547670Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018317)
Ref 548077Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021743)
Ref 548134Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022281)
Ref 548211Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023138)
Ref 548244Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023697)
Ref 548427Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025519)
Ref 548691Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027710)
Ref 549860Clinical pipeline report, company report or official report of Incyte.
Ref 527121J Nat Prod. 2004 Jun;67(6):1036-8.Isolation and structure of antagonists of chemokine receptor (CCR5).
Ref 527257J Nat Prod. 2004 Oct;67(10):1681-4.Inhibition of the human chemokine receptor CCR5 by variecolin and variecolol and isolation of four new variecolin analogues, emericolins A-D, from Emericella aurantiobrunnea.
Ref 528341J Nat Prod. 2006 Jul;69(7):1025-8.Chemokine receptor CCR-5 inhibitors produced by Chaetomium globosum.
Ref 528511Bioorg Med Chem Lett. 2007 Jan 1;17(1):231-4. Epub 2006 Nov 1.CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives.
Ref 528689Bioorg Med Chem Lett. 2007 Apr 1;17(7):1883-7. Epub 2007 Jan 25.CCR5 receptor antagonists: discovery and SAR of novel 4-hydroxypiperidine derivatives.
Ref 529307Bioorg Med Chem Lett. 2008 Mar 15;18(6):2000-5. Epub 2008 Feb 2.Reduced cardiac side-effect potential by introduction of polar groups: discovery of NIBR-1282, an orally bioavailable CCR5 antagonist which is active in vivo.
Ref 529636Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clin Ther. 2008 Jul;30(7):1228-50.
Ref 530181Tapping into combination pills for HIV. Nat Rev Drug Discov. 2009 Jun;8(6):439-40.
Ref 531280An 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 531384Agonist-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 531584Determination of nifeviroc, a novel CCR5 antagonist: application to a pharmacokinetic study. J Pharm Biomed Anal. 2011 Nov 1;56(3):637-40.
Ref 531630A dual CCR2/CCR5 chemokine antagonist, BMS-813160. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.
Ref 531985The 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 533043The 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 533257Preclinical 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 534846Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell. 1999 Mar 5;96(5):667-76.
Ref 536143Progress in targeting HIV-1 entry. Drug Discov Today. 2005 Aug 15;10(16):1085-94.
Ref 536516Species selectivity of small-molecular antagonists for the CCR5 chemokine receptor. Int Immunopharmacol. 2007 Dec 5;7(12):1528-34. Epub 2007 Aug 14.
Ref 536797In 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. Epub 2008 Aug 1.
Ref 537430Rapamycin enhances aplaviroc anti-HIV activity: implications for the clinical development of novel CCR5 antagonists. Antiviral Res. 2009 Jul;83(1):86-9. Epub 2009 Mar 9.
Ref 537478HIV entry: new insights and implications for patient management. Curr Opin Infect Dis. 2009 Feb;22(1):35-42.
Ref 537962Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996 Mar 19;35(11):3362-7.
Ref 540496(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: 3651).
Ref 544105CCR5 Monoclonal Antibodies for HIV-1 Therapy. Curr Opin HIV AIDS. 2009 March; 4(2): 104-111.
Ref 544423Gene 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 548078Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021743)
Ref 550288Clinical pipeline report, company report or official report of AstraZeneca (2009).
Ref 551022Incyte. Product Development Pipeline.

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