Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7HQD0)

• DTT Name: C-C chemokine receptor type 4 (CCR4)
• Synonyms: K5-5; CMKBR4; CD194; CCR-4; CC-CKR-4; CC chemokine receptor 4; C-CCKR-4; C-C CKR-4
• Gene Name: CCR4
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: CCR4_HUMAN
• TTD ID: T06955
• Sequence:
  MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGELFLPPLYSLVFVFGLLGNSVV
  VLVLFKYKRLRSMTDVYLLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMISWMYLVG
  FYSGIFFVMLMSIDRYLAIVHAVFSLRARTLTYGVITSLATWSVAVFASLPGFLFSTCYT
  ERNHTYCKTKYSLNSTTWKVLSSLEINILGLVIPLGIMLFCYSMIIRTLQHCKNEKKNKA
  VKMIFAVVVLFLGFWTPYNIVLFLETLVELEVLQDCTFERYLDYAIQATETLAFVHCCLN
  PIIYFFLGEKFRKYILQLFKTCRGLFVLCQYCGLLQIYSADTPSSSYTQSTMDHDLHDAL
• Function: The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second 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. High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine signaling pathway (hsa04062)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mogamulizumab	DMISH0Z	Mycosis fungoides	2B01	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RPT193	DMZJ0N3	Asthma	CA23	Phase 2	[2]
FLX475	DMI7S39	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[3]
ATLCAR.CD30.CCR4 cells	DM3IPSX	Immune System disease	4A01-4B41	Phase 1	[4]
GSK-2239633	DMUNVXR	Asthma	CA23	Phase 1	[5]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD-1678	DMY7R3X	Asthma	CA23	Preclinical	[6]

16 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-isopropyl-N-(naphthalen-1-yl)thiazol-2-amine	DMW1T93	Discovery agent	N.A.	Investigative	[7]
4-methyl-N-(naphthalen-1-yl)thiazol-2-amine	DMFRASQ	Discovery agent	N.A.	Investigative	[7]
4-tert-butyl-N-(2-isopropylphenyl)thiazol-2-amine	DMDWRE5	Discovery agent	N.A.	Investigative	[7]
4-tert-butyl-N-(naphthalen-1-yl)oxazol-2-amine	DM5U6ZW	Discovery agent	N.A.	Investigative	[7]
4-tert-butyl-N-(naphthalen-1-yl)thiazol-2-amine	DMBUZ75	Discovery agent	N.A.	Investigative	[7]
4-tert-butyl-N-m-tolylthiazol-2-amine	DM9K27Q	Discovery agent	N.A.	Investigative	[7]
4-tert-butyl-N-o-tolylthiazol-2-amine	DMJQFD5	Discovery agent	N.A.	Investigative	[7]
4-tert-butyl-N-phenylthiazol-2-amine	DM5CPBK	Discovery agent	N.A.	Investigative	[7]
AT-008	DMODLPS	Autoimmune diabetes	5A10	Investigative	[5]
C-014C	DMD7OQA	Discovery agent	N.A.	Investigative	[8]
N-(4-tert-butylthiazol-2-yl)-1H-indol-4-amine	DMFUBQ8	Discovery agent	N.A.	Investigative	[7]
N-(4-tert-butylthiazol-2-yl)isoquinolin-5-amine	DMMUX86	Discovery agent	N.A.	Investigative	[7]
N-(4-tert-butylthiazol-2-yl)quinolin-5-amine	DMBMAKG	Discovery agent	N.A.	Investigative	[7]
N-(naphthalen-1-yl)-4-neopentylthiazol-2-amine	DMW378C	Discovery agent	N.A.	Investigative	[7]
N-(naphthalen-1-yl)-4-phenylthiazol-2-amine	DMFZPCD	Discovery agent	N.A.	Investigative	[7]
RS-1748	DM9D8XC	Asthma	CA23	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	5.82E-01	-0.04	-0.07
Atopic dermatitis	EA90	Skin	2.33E-02	3.98E-03	0.03

References

• [1] Mogamulizumab, a humanized mAb against C-C chemokine receptor 4 for the potential treatment of T-cell lymphomas and asthma. Curr Opin Mol Ther. 2010 Dec;12(6):770-9.
• [2] ClinicalTrials.gov (NCT05399368) A Phase 2 Study to Evaluate the Efficacy and Safety of RPT193 as Monotherapy in Adults With Moderate-to-Severe Atopic Dermatitis. U.S.National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT03602157) Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and NHL
• [5] 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. (Target id: 61).
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030818)
• [7] Optimization of 2-aminothiazole derivatives as CCR4 antagonists. Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3.
• [8] Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines. Bioorg Med Chem. 2008 Jul 15;16(14):7021-32.