| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T96079 | ||||
| Target Name | C-X-C chemokine receptor type 4 (CXCR4) | ||||
| Type of Target |
Successful |
||||
| Drug Potency against Target | Plerixafor | Drug Info | IC50 = 1~2 nM | [4] | |
| Cyclo(-D-Ala-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 130 nM | [1] | ||
| Cyclo(-D-MeTyr-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 157 nM | [1] | ||
| Cyclo(-D-MeTyr-L-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 128 nM | [1] | ||
| Cyclo(-D-Tyr-Arg-Arg-Nal-Gly-) | Drug Info | IC50 = 35 nM | [3] | ||
| Cyclo(-D-Tyr-D-Ala-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 230 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-MeNal-Gly-) | Drug Info | IC50 = 563 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-beta-Ala-) | Drug Info | IC50 = 350 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-D-Ala-) | Drug Info | IC50 = 11 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 8 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-L-Ala-) | Drug Info | IC50 = 92 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-L-Pic-) | Drug Info | IC50 = 640 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-Sar-) | Drug Info | IC50 = 256 nM | [1] | ||
| Cyclo(-D-Tyr-D-Arg-L-MeArg-L-Nal-Gly-) | Drug Info | IC50 = 21 nM | [1] | ||
| Cyclo(-D-Tyr-D-MeArg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 3 nM | [1] | ||
| Cyclo(-D-Tyr-L-Ala-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 63 nM | [1] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Ala-Sar-) | Drug Info | IC50 = 167 nM | [1] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-MeNal-Gly-) | Drug Info | IC50 = 250 nM | [1] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-beta-Ala-) | Drug Info | IC50 = 47 nM | [1] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-D-Ala-) | Drug Info | IC50 = 11 nM | [1] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 4 nM | [1] | ||
| Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-L-Ala-) | Drug Info | IC50 = 170 nM | [1] | ||
| Cyclo(-D-Tyr-L-Arg-L-MeArg-L-Nal-Gly-) | Drug Info | IC50 = 99 nM | [1] | ||
| Cyclo(-D-Tyr-L-MeArg-L-Arg-L-Nal-Gly-) | Drug Info | IC50 = 23 nM | [1] | ||
| TN-14003 | Drug Info | IC50 = 0.6 nM | [2] | ||
| Action against Disease Model | Plerixafor | Drug Info | 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. | [5] | |
| References | |||||
| REF 1 | Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone... J Med Chem. 2007 Jan 25;50(2):192-8. | ||||
| REF 2 | Discovery of small molecule CXCR4 antagonists. J Med Chem. 2007 Nov 15;50(23):5655-64. | ||||
| REF 3 | Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach. Bioorg Med Chem Lett. 2008 Jul 15;18(14):4124-9. | ||||
| REF 4 | Chemokine receptor-directed agents as novel anti-HIV-1 therapies. Curr Top Med Chem. 2004;4(10):1017-33. | ||||
| REF 5 | 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. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.