| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T96079 | ||||
| Target Name | C-X-C chemokine receptor 4 | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Plerixafor | Drug Info | IC50 = 1~2 nM | [552440] | |
| Cyclo(-D-Tyr-L-Ala-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 63 nM | [528618] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-D-Ala-) | Drug Info | IC50 = 11 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-beta-Ala-) | Drug Info | IC50 = 350 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-L-Pic-) | Drug Info | IC50 = 640 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-Sar-) | Drug Info | IC50 = 256 nM | [528618] | ||
| Cyclo(-D-Tyr-L-MeArg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 23 nM | [528618] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 4 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-L-Ala-) | Drug Info | IC50 = 92 nM | [528618] | ||
| Cyclo(-D-MeTyr-L-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 128 nM | [528618] | ||
| Cyclo(-D-Tyr-D-MeArg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 3 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-MeArg-L-Nal-Gly-) | Drug Info | IC50 = 21 nM | [528618] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-L-Ala-) | Drug Info | IC50 = 170 nM | [528618] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-beta-Ala-) | Drug Info | IC50 = 47 nM | [528618] | ||
| Cyclo(-D-Ala-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 130 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 8 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Ala-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 230 nM | [528618] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-MeNal-Gly-) | Drug Info | IC50 = 250 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-MeNal-Gly-) | Drug Info | IC50 = 563 nM | [528618] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-D-Ala-) | Drug Info | IC50 = 11 nM | [528618] | ||
| TN-14003 | Drug Info | IC50 = 0.6 nM | [529115] | ||
| Cyclo(-D-Tyr-L-Arg-L-MeArg-L-Nal-Gly-) | Drug Info | IC50 = 99 nM | [528618] | ||
| Cyclo(-D-MeTyr-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 157 nM | [528618] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Ala-Sar-) | Drug Info | IC50 = 167 nM | [528618] | ||
| Cyclo(-D-Tyr-Arg-Arg-Nal-Gly-) | Drug Info | IC50 = 35 nM | [529526] | ||
| Action against Disease Model | Plerixafor | By efficient CXCR4 blocking in the CXCR4(+)/BCR-ABL(+) cell line BV-173, plerixafor (1-100 m uM) significantly inhibits SDF-1alpha-mediated chemotaxis and cell migration toward the murine stroma cell line FBMD-1. Furthermore, plerixafor also significantly (10-100 m uM) increased the detachment rate of SDF-1-mediated/VCAM-1-associated cell adherence under shear stress. Using a stroma-dependent coculture assay, plerixafor sensitized BCR-ABL(+) cells toward tyrosine kinase inhibitor therapy. | [552967] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | We investigated the role of CXCR4 in osteoclastogenesis and in a model of bone metastasis. Compared with controls, mice reconstituted with CXCR4 null hematopoietic cells exhibited elevated markers of bone resorption, increased OC perimeter along bone, and increased bone loss. CXCR4-/- OCs demonstrated accelerated differentiation and enhanced bone resorption in vitro. Furthermore, t uMor growth specifically in bone was significantly increased in mice reconstituted with CXCR4-/- hematopoietic cells. Finally, enhancement of bone t uMor growth in the absence of CXCR4 was abrogated with the OC inhibitor, zoledronic acid. These data demonstrate that disruption of CXCR4 enhances osteoclastogenesis and suggest that inhibition of CXCR4 may enhance established skeletal t uMor burden by increasing OC activity. | [552440] | |||
| References | |||||
| Ref 552440 | Chemokine receptor-directed agents as novel anti-HIV-1 therapies. Curr Top Med Chem. 2004;4(10):1017-33. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 552967 | Plerixafor inhibits chemotaxis toward SDF-1 and CXCR4-mediated stroma contact in a dose-dependent manner resulting in increased susceptibility of BCR-ABL+ cell to Imatinib and Nilotinib. Leuk Lymphoma. 2009 Oct;50(10):1676-86. doi: 10.1080/10428190903150847. | ||||
| Ref 529115 | J Med Chem. 2007 Nov 15;50(23):5655-64. Epub 2007 Oct 24.Discovery of small molecule CXCR4 antagonists. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 528618 | J Med Chem. 2007 Jan 25;50(2):192-8.Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. | ||||
| Ref 529526 | Bioorg Med Chem Lett. 2008 Jul 15;18(14):4124-9. Epub 2008 May 29.Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach. | ||||
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