Target Information

Target General Infomation
Target ID
T06955
Former ID
TTDC00226
Target Name
C-Cchemokine receptor type 4
Gene Name
CCR4
Synonyms
C-CCKR-4; CC chemokine receptor 4; CC-CKR-4; CCR-4; K5-5; CCR4
Target Type
Clinical Trial
Disease Atopic dermatitis [ICD9: 691.8, 692.9; ICD10: L00-L99]
Autoimmune diabetes [ICD10: E08-E13]
Asthma [ICD10: J45]
Function
High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calciumsecond messenger system. Can function as a chemoattractant homing receptor on circulating memory lymphocytes and as a coreceptor for some primary HIV-2 isolates. In the CNS, could mediate hippocampal-neuron survival.
BioChemical Class
GPCR rhodopsin
Target Validation
T06955
UniProt ID
P51679
Sequence
MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGELFLPPLYSLVFVFGLLGNSVV
VLVLFKYKRLRSMTDVYLLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMISWMYLVG
FYSGIFFVMLMSIDRYLAIVHAVFSLRARTLTYGVITSLATWSVAVFASLPGFLFSTCYT
ERNHTYCKTKYSLNSTTWKVLSSLEINILGLVIPLGIMLFCYSMIIRTLQHCKNEKKNKA
VKMIFAVVVLFLGFWTPYNIVLFLETLVELEVLQDCTFERYLDYAIQATETLAFVHCCLN
PIIYFFLGEKFRKYILQLFKTCRGLFVLCQYCGLLQIYSADTPSSSYTQSTMDHDLHDAL
Drugs and Mode of Action
Drug(s) Mogamulizumab Drug Info Phase 2 Discovery agent [523931], [541612]
GSK-2239633 Drug Info Phase 1 Asthma [522973]
AZD-1678 Drug Info Preclinical Asthma [548958]
Inhibitor 4-isopropyl-N-(naphthalen-1-yl)thiazol-2-amine Drug Info [528047]
4-methyl-N-(naphthalen-1-yl)thiazol-2-amine Drug Info [528047]
4-tert-butyl-N-(2-isopropylphenyl)thiazol-2-amine Drug Info [528047]
4-tert-butyl-N-(naphthalen-1-yl)oxazol-2-amine Drug Info [528047]
4-tert-butyl-N-(naphthalen-1-yl)thiazol-2-amine Drug Info [528047]
4-tert-butyl-N-m-tolylthiazol-2-amine Drug Info [528047]
4-tert-butyl-N-o-tolylthiazol-2-amine Drug Info [528047]
4-tert-butyl-N-phenylthiazol-2-amine Drug Info [528047]
C-014C Drug Info [529524]
Mogamulizumab Drug Info [531298]
N-(4-tert-butylthiazol-2-yl)-1H-indol-4-amine Drug Info [528047]
N-(4-tert-butylthiazol-2-yl)isoquinolin-5-amine Drug Info [528047]
N-(4-tert-butylthiazol-2-yl)quinolin-5-amine Drug Info [528047]
N-(naphthalen-1-yl)-4-neopentylthiazol-2-amine Drug Info [528047]
N-(naphthalen-1-yl)-4-phenylthiazol-2-amine Drug Info [528047]
Antagonist AT-008 Drug Info [543896]
AZD-1678 Drug Info [548959]
CCR4 antagonists Drug Info [543896]
GSK-2239633 Drug Info [543896]
Modulator RS-1748 Drug Info [543896]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
Chemokine signaling pathway
Viral carcinogenesis
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
Reactome Chemokine receptors bind chemokines
G alpha (i) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
Ref 522973ClinicalTrials.gov (NCT01086462) Intravenous Microdose Pharmacokinetic (PK) Study With [14C]-GSK2239633. U.S. National Institutes of Health.
Ref 523931ClinicalTrials.gov (NCT01611142) Study of KW-0761 (Mogamulizumab) in Subjects With Previously Treated Peripheral T-cell Lymphoma (PTCL). U.S. National Institutes of Health.
Ref 541612(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: 6477).
Ref 548958Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030818)
Ref 528047Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. Epub 2006 Feb 23.Optimization of 2-aminothiazole derivatives as CCR4 antagonists.
Ref 529524Bioorg Med Chem. 2008 Jul 15;16(14):7021-32. Epub 2008 May 20.Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines.
Ref 531298Curr Opin Mol Ther. 2010 Dec;12(6):770-9.Mogamulizumab, a humanized mAb against C-C chemokine receptor 4 for the potential treatment of T-cell lymphomas and asthma.
Ref 543896(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: 61).
Ref 548959Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030818)

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