Target Information

Target General Infomation
Target ID
T89988
Former ID
TTDC00122
Target Name
C-C chemokine receptor type 2
Gene Name
CCR2
Synonyms
C-C CKR-2; CC-CKR-2; CCR-2; Chemokine receptor CCR2B; MCP-1-R; Monocyte chemoattractant protein 1 receptor; CCR2
Target Type
Clinical Trial
Disease Arthritis [ICD9: 710-719; ICD10: M00-M25]
Atherosclerosis [ICD9: 414.0, 440; ICD10: I70]
Arteriosclerosis [ICD9: 440; ICD10: I70]
Alzheimer disease [ICD9: 331; ICD10: G30]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Diabetic nephropathy [ICD9: 250.4; ICD10: E11.21]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Multiple scierosis [ICD9: 340; ICD10: G35]
Metastatic cancer; Multiple scierosis [ICD9:140-199, 140-229, 210-229, 340; ICD10: D10-D36, D3A, G35]
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0]
Obese insulin-resistant disorders; Rheumatoid arthritis [ICD9:250, 710-719, 714; ICD10: E11, M05-M06]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Receptor for the CCL2, CCL7 and CCL13 chemokines. Transduces a signal by increasing intracellular calcium ion levels. Alternative coreceptor with CD4 for HIV-1 infection.
BioChemical Class
GPCR rhodopsin
Target Validation
T89988
UniProt ID
P41597
Sequence
MLSTSRSRFIRNTNESGEEVTTFFDYDYGAPCHKFDVKQIGAQLLPPLYSLVFIFGFVGN
MLVVLILINCKKLKCLTDIYLLNLAISDLLFLITLPLWAHSAANEWVFGNAMCKLFTGLY
HIGYFGGIFFIILLTIDRYLAIVHAVFALKARTVTFGVVTSVITWLVAVFASVPGIIFTK
CQKEDSVYVCGPYFPRGWNNFHTIMRNILGLVLPLLIMVICYSGILKTLLRCRNEKKRHR
AVRVIFTIMIVYFLFWTPYNIVILLNTFQEFFGLSNCESTSQLDQATQVTETLGMTHCCI
NPIIYAFVGEKFRSLFHIALGCRIAPLQKPVCGGPGVRPGKNVKVTTQGLLDGRGKGKSI
GRAPEASLQDKEGA
Structure
1KAD; 1KP1
Drugs and Mode of Action
Drug(s) BMS-813160 Drug Info Phase 2 Diabetic nephropathy [524165]
CCX-140 Drug Info Phase 2 Diabetic nephropathy [547696]
MK-0812 Drug Info Phase 2 Multiple scierosis [521746]
MLN1202 Drug Info Phase 2 Metastatic cancer; Multiple scierosis [537520]
CCX872 Drug Info Phase 1 Diabetic nephropathy [525071]
OPL-CCL2-LPM Drug Info Phase 1 Arthritis [548903]
MCP-1 Drug Info Preclinical Rheumatoid arthritis [536223]
RS-504393 Drug Info Preclinical Chronic obstructive pulmonary disease [536223], [542757]
AZD-2423 Drug Info Discontinued in Phase 2 Chronic obstructive pulmonary disease [523197], [542770]
INCB3284 Drug Info Discontinued in Phase 2 Obese insulin-resistant disorders; Rheumatoid arthritis [547666]
CCX915 Drug Info Discontinued in Phase 1 Multiple scierosis [549358]
INCB8696 Drug Info Discontinued in Phase 1 Multiple scierosis [548303]
AZD-6942 Drug Info Terminated Rheumatoid arthritis [547438]
INCB3344 Drug Info Terminated Arteriosclerosis [542721], [549359]
SB-282241 Drug Info Terminated Inflammatory disease [526712], [542764]
Inhibitor (R)-3-(1'-Adamantanecarbonyl)amino-caprolactam Drug Info [530113]
(S)-3-(1'-Adamantanecarbonyl)amino-caprolactam Drug Info [530113]
(S)-3-(2',2'-Dimethyl-propionyl)amino-caprolactam Drug Info [530113]
CCX872 Drug Info [551637]
NSC-651016 Drug Info [534649]
Antagonist AZD-2423 Drug Info [550850]
AZD-6942 Drug Info [550879]
BMS-A Drug Info [543887]
CCX-140 Drug Info [533233]
CCX915 Drug Info [550191]
GSK Compound 34 Drug Info [543887]
GSK-1344386B Drug Info [543887]
INCB-10820 Drug Info [543887]
INCB3284 Drug Info [550211]
INCB3344 Drug Info [531362]
INCB8696 Drug Info [551022]
MCP-1 Drug Info [536223]
MK-0812 Drug Info [530515]
MLN1202 Drug Info [536223]
RS-102895 Drug Info [525750]
RS-136270 Drug Info [525750]
RS-504393 Drug Info [536223], [536550]
SB-282241 Drug Info [550879]
Teijin-lead_cmp_5 Drug Info [526712]
viral macrophage inflammatory protein-II Drug Info [534456]
Modulator BMS-813160 Drug Info [531630]
OPL-CCL2-LPM Drug Info [544075]
RAP-103 Drug Info [543887]
RAP-310 Drug Info [543887]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
Chemokine signaling pathway
NetPath Pathway TCR Signaling Pathway
IL2 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
Leptin Signaling Pathway
RANKL Signaling Pathway
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
Reactome Beta defensins
Chemokine receptors bind chemokines
G alpha (i) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Defensins
Spinal Cord Injury
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
Ref 521746ClinicalTrials.gov (NCT00239655) A Study to Assess the Effects of MK0812 on Disease Activity in Patients With Relapsing-Remitting Multiple Sclerosis as Measured by Magnetic Resonance Imaging (MRI). U.S. National Institutes of Health.
Ref 523197ClinicalTrials.gov (NCT01215279) AZD2423 Safety and Tolerability Study in Patients With Moderate and Severe Chronic Obstructive Pulmonary Disease(COPD). 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 525071ClinicalTrials.gov (NCT02345408) Phase 1b Study of CCX872-B in Patients With Pancreatic Adenocarcinoma. U.S. National Institutes of Health.
Ref 526712CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach. J Med Chem. 2003 Sep 11;46(19):4070-86.
Ref 536223Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
Ref 537520Emerging drugs for the therapy of primary and post essential thrombocythemia, post polycythemia vera myelofibrosis. Expert Opin Emerg Drugs. 2009 Jun 24.
Ref 542721(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: 777).
Ref 542757(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: 781).
Ref 542764(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: 782).
Ref 542770(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: 7825).
Ref 547438Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016328)
Ref 547666Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018258)
Ref 547696Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018498)
Ref 548303Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024340)
Ref 548903Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030092)
Ref 549358Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035649)
Ref 549359Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035662)
Ref 525750J Biol Chem. 2000 Aug 18;275(33):25562-71.Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helicalbundle.
Ref 526712CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach. J Med Chem. 2003 Sep 11;46(19):4070-86.
Ref 530113J Med Chem. 2009 Jun 11;52(11):3591-5.Highly potent, orally available anti-inflammatory broad-spectrum chemokine inhibitors.
Ref 530515Assessment of chemokine receptor function on monocytes in whole blood: In vitro and ex vivo evaluations of a CCR2 antagonist. J Immunol Methods. 2010 Jan 31;352(1-2):101-10.
Ref 531362Discovery of ((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone, PF-4254196, a CCR2 antagonist with an improved cardiovascular profile. Bioorg Med Chem Lett. 2011 May 1;21(9):2626-30.
Ref 531630A dual CCR2/CCR5 chemokine antagonist, BMS-813160. Expert Opin Ther Pat. 2011 Dec;21(12):1919-24.
Ref 533233Present and future in the treatment of diabetic kidney disease. J Diabetes Res. 2015;2015:801348.
Ref 534456A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science. 1997 Sep 12;277(5332):1656-9.
Ref 534649J Med Chem. 1998 Jun 18;41(13):2184-93.Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that interferes with chemokine receptor function: a candidate for chemotherapeutic and microbicidal application.
Ref 536223Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
Ref 536550Beneficial or detrimental effects of carotenoids contained in food: cell culture models. Mini Rev Med Chem. 2007 Nov;7(11):1120-8.
Ref 543887(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. (Target id: 59).
Ref 544075Selective CCR2-targeted macrophage depletion ameliorates experimental mesangioproliferative glomerulonephritis. Clin Exp Immunol. 2009 February; 155(2): 295-303.
Ref 550191Marketed and experimental medicines for the treatment of multiple sclerosis. The Association of the British Pharmaceutical Industry. 2009.
Ref 550211Incyte Announces Second Quarter 2005 Financial Results; Reports Positive Phase IIb Results for Reverset in Treatment-Experienced HIV Patients. Incyte Corporation. 2005.
Ref 550850CA patent application no. 841416, Method of selecting therapeutic indications.
Ref 550879Patent EP2727944 A1.
Ref 551022Incyte. Product Development Pipeline.
Ref 551637Therapeutic use of a clinical stage CCR2 inhibitor, CCX872, in obesity-associated steatohepatitis. The Lancet Volume 383, Supplement 1, 26 February 2014, Pages S78.

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