Target Validation Information
Target ID T06955
Target Name C-Cchemokine receptor type 4
Target Type
Clinical Trial
Drug Potency against Target 4-isopropyl-N-(naphthalen-1-yl)thiazol-2-amine Drug Info IC50 = 170 nM [528047]
4-tert-butyl-N-m-tolylthiazol-2-amine Drug Info IC50 = 2000 nM [528047]
N-(4-tert-butylthiazol-2-yl)-1H-indol-4-amine Drug Info IC50 = 490 nM [528047]
C-014C Drug Info IC50 = 13 nM [529524]
Cenicriviroc Drug Info IC50 = 1100 nM [528083]
N-(naphthalen-1-yl)-4-neopentylthiazol-2-amine Drug Info IC50 = 220 nM [528047]
4-tert-butyl-N-phenylthiazol-2-amine Drug Info IC50 = 4500 nM [528047]
4-tert-butyl-N-o-tolylthiazol-2-amine Drug Info IC50 = 900 nM [528047]
4-methyl-N-(naphthalen-1-yl)thiazol-2-amine Drug Info IC50 = 6400 nM [528047]
4-tert-butyl-N-(naphthalen-1-yl)oxazol-2-amine Drug Info IC50 = 80 nM [528047]
N-(4-tert-butylthiazol-2-yl)quinolin-5-amine Drug Info IC50 = 300 nM [528047]
N-(4-tert-butylthiazol-2-yl)isoquinolin-5-amine Drug Info IC50 = 1500 nM [528047]
4-tert-butyl-N-(2-isopropylphenyl)thiazol-2-amine Drug Info IC50 = 440 nM [528047]
4-tert-butyl-N-(naphthalen-1-yl)thiazol-2-amine Drug Info IC50 = 80 nM [528047]
N-(naphthalen-1-yl)-4-phenylthiazol-2-amine Drug Info IC50 = 5500 nM [528047]
Action against Disease Model Mogamulizumab Mogamuliz uMab reduced t uMor load via enhanced antibody-dependent cell cytotoxicity in preclinical studies and demonstrated promising efficacy in early clinical trials in patients with ATL. In addition, CCR4 also has a role in maintaining T-helper cell type 2 airways inflammation in asthma, and Amgen have acquired the rights to develop mogamuliz uMab for this indication andother non-oncology indications [531298] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations This study investigates the role of chemokine receptor 4 (CCR4) in acute and chronic cardiac allograft rejection in mice. Allogeneic hearts were transplanted into CCR4 deficient(CCR4(-/-)) and control recipients. Reverse transcription-PCR showed transcription of macrophage-derived chemokine and thymus and activation-regulated chemokine, the cognate chemokine ligands of CCR4, within the graft. Compared to wild-type controls, acute allograft rejection in CCR4(-/-) recipients was only slightly prolonged. In contrast, in a galli uM nitrate chronic cardiac allograft rejection model, cardiac graft survival was significantly prolonged in CCR4(-/-) recipients. A relative increase in the percentage of graft infiltrating CD8(+) T cells in CCR4(-/-) recipients was observed 30 days after transplantation and was accompanied by a decrease in CD4(+) T cells. Moreover, the percentage of NK1.1(+)CD3(+) graft-infiltrating cells was significantly reduced on day 5 and day 30 post transplantation. These findings indicate that CCR4 is involved in the recruitment of NK1.1(+)CD3(+) cells into cardiac allografts and clearly establish an important and novel role for CCR4 in chronic graft rejection. [531298]
References
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 528047Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. Epub 2006 Feb 23.Optimization of 2-aminothiazole derivatives as CCR4 antagonists.
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 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 528083J Med Chem. 2006 Mar 23;49(6):2037-48.Highly potent and orally active CCR5 antagonists as anti-HIV-1 agents: synthesis and biological activities of 1-benzazocine derivatives containing a sulfoxide moiety.
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 528047Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. Epub 2006 Feb 23.Optimization of 2-aminothiazole derivatives as CCR4 antagonists.
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 528047Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. Epub 2006 Feb 23.Optimization of 2-aminothiazole derivatives as CCR4 antagonists.
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 528047Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. Epub 2006 Feb 23.Optimization of 2-aminothiazole derivatives as CCR4 antagonists.
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 528047Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. Epub 2006 Feb 23.Optimization of 2-aminothiazole derivatives as CCR4 antagonists.
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 528047Bioorg Med Chem Lett. 2006 May 15;16(10):2800-3. Epub 2006 Feb 23.Optimization of 2-aminothiazole derivatives as CCR4 antagonists.

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