Target Information
Target General Infomation | |||||
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Target ID |
T96079
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Former ID |
TTDC00121
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Target Name |
C-X-C chemokine receptor 4
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Gene Name |
CXCR4
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Synonyms |
CD184 antigen; CXC-R4; CXCR-4; Chemokine receptor CXCR4; FB22; Fusin; HM89; LCR1; LESTR; Leukocyte-derived seven transmembrane domain receptor; NPYRL; SDF-1 receptor; Stromal cell-derived factor 1 receptor; CXCR4
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Target Type |
Successful
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Disease | Acute lymphoblastic leukemia [ICD9: 204.0, 556; ICD10: C91.0] | ||||
Acute myeloid leukemia; B-cell chronic lymphocytic leukemia [ICD9: 202.8, 203.0, 204.1, 205.0, 208.9; ICD10: C81-C86, C90.0, C91-C95, C91.1, C92.0] | |||||
Autoimmune diabetes [ICD10: E08-E13] | |||||
Acute myeloid leukemia [ICD9: 205; ICD10: C92.0] | |||||
Bone marrow transplantation [ICD9: 279.5, 996; ICD10: D89.8, T86] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
HIV-1 infection [ICD9: 001-139, 042; ICD10: B20-B24] | |||||
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26] | |||||
Human immunodeficiency virus infection; Non-hodgkin's lymphoma; Late-stage solid tumors [ICD9:279.3, 140-199, 200, 202, 202.8, 210-229; ICD10: B20-B26, C00-C75, C7A, C7B, C81-C86, C82-C85, D10-D36, D3A] | |||||
Hematological malignancies [ICD9: 200-209; ICD10: C81-C86] | |||||
Hematopoietic [ICD10: D50-D89] | |||||
Macular degeneration [ICD9: 362.5; ICD10: H35.3] | |||||
Peripheral vascular disease [ICD9: 443.9; ICD10: I73.9] | |||||
Sarcoma [ICD9: 202.8; ICD10: C81-C86] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T96079
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UniProt ID | |||||
Sequence |
MEGISIYTSDNYTEEMGSGDYDSMKEPCFREENANFNKIFLPTIYSIIFLTGIVGNGLVI
LVMGYQKKLRSMTDKYRLHLSVADLLFVITLPFWAVDAVANWYFGNFLCKAVHVIYTVNL YSSVLILAFISLDRYLAIVHATNSQRPRKLLAEKVVYVGVWIPALLLTIPDFIFANVSEA DDRYICDRFYPNDLWVVVFQFQHIMVGLILPGIVILSCYCIIISKLSHSKGHQKRKALKT TVILILAFFACWLPYYIGISIDSFILLEIIKQGCEFENTVHKWISITEALAFFHCCLNPI LYAFLGAKFKTSAQHALTSVSRGSSLKILSKGKRGGHSSVSTESESSSFHSS |
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Structure |
1ILP; 1ILQ; 2LNL; 2K03; 2K04; 2K05; 3ODU; 3OE0; 3OE6; 3OE8; 3OE9
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Drugs and Mode of Action | |||||
Drug(s) | Plerixafor | Drug Info | Approved | Human immunodeficiency virus infection; Non-hodgkin's lymphoma; Late-stage solid tumors | [529941], [537114], [543136] |
BL-8040 | Drug Info | Phase 2 | Acute myeloid leukemia | [525271] | |
POL-6326 | Drug Info | Phase 2 | Human immunodeficiency virus infection | [523007] | |
TG-0054 | Drug Info | Phase 2 | Macular degeneration | [522865] | |
AMD-070 | Drug Info | Phase 1/2 | Human immunodeficiency virus infection | [521607], [543204] | |
CTCE-9908 | Drug Info | Phase 1/2 | Sarcoma | [530179] | |
ALX-0651 | Drug Info | Phase 1 | Hematological malignancies | [523519] | |
BMS-936564 | Drug Info | Phase 1 | Acute myeloid leukemia; B-cell chronic lymphocytic leukemia | [525014] | |
CTCE-0214 | Drug Info | Phase 1 | Hematopoietic | [548105] | |
LY-2624587 | Drug Info | Phase 1 | Cancer | [523067] | |
MSX-122 | Drug Info | Phase 1 | Solid tumours | [548672] | |
Garnocestim | Drug Info | Discontinued in Phase 1 | Bone marrow transplantation | [546869] | |
SURADISTA | Drug Info | Discontinued in Phase 1 | Solid tumours | [545728] | |
KRH-2731 | Drug Info | Terminated | Human immunodeficiency virus infection | [547903] | |
Inhibitor | ALX-0651 | Drug Info | [544156] | ||
Cyclo(-D-Ala-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-MeTyr-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-MeTyr-L-Arg-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-Arg-Arg-Nal-Gly-) | Drug Info | [529526] | |||
Cyclo(-D-Tyr-D-Ala-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-Arg-L-MeNal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-beta-Ala-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-D-Ala-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-L-Ala-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-L-Pic-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-Arg-L-Nal-Sar-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-Arg-L-MeArg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-D-MeArg-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Ala-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Arg-L-Arg-L-Ala-Sar-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Arg-L-Arg-L-MeNal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-beta-Ala-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-D-Ala-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Arg-L-Arg-L-Nal-L-Ala-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-Arg-L-MeArg-L-Nal-Gly-) | Drug Info | [528618] | |||
Cyclo(-D-Tyr-L-MeArg-L-Arg-L-Nal-Gly-) | Drug Info | [528618] | |||
ND-401 | Drug Info | [543930] | |||
TG-0054 | Drug Info | [532779] | |||
TN-14003 | Drug Info | [529115] | |||
Antagonist | AMD-070 | Drug Info | [536630], [536663] | ||
AT-009 | Drug Info | [543930] | |||
BL-8040 | Drug Info | [550382] | |||
GSK-812397 | Drug Info | [543930] | |||
isothiourea-1a | Drug Info | [529840] | |||
isothiourea-1t | Drug Info | [529840] | |||
LP-0067 | Drug Info | [543930] | |||
MSX-122 | Drug Info | [535860] | |||
Plerixafor | Drug Info | [537114] | |||
POL-6326 | Drug Info | [531821] | |||
T134 | Drug Info | [534819] | |||
T140 | Drug Info | [534819] | |||
T22 | Drug Info | [534819] | |||
viral macrophage inflammatory protein-II | Drug Info | [534456] | |||
Agonist | ATI-2341 | Drug Info | [543930] | ||
CTCE-0214 | Drug Info | [531347] | |||
CXCL8 | Drug Info | [527153] | |||
Modulator | BMS-936564 | Drug Info | [532141] | ||
CTCE-0324 | Drug Info | [543930] | |||
CTCE-9908 | Drug Info | [530179] | |||
CXCR4 gene disrupted T cells | Drug Info | [543930] | |||
Garnocestim | Drug Info | [551900] | |||
KUR-CXCR4 | Drug Info | [543930] | |||
NB-325 | Drug Info | [543930] | |||
SURADISTA | Drug Info | [526483] | |||
Binder | KRH-2731 | Drug Info | [536143] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Cytokine-cytokine receptor interaction | ||||
Chemokine signaling pathway | |||||
Endocytosis | |||||
Axon guidance | |||||
Leukocyte transendothelial migration | |||||
Intestinal immune network for IgA production | |||||
Pathways in cancer | |||||
NetPath Pathway | IL2 Signaling Pathway | ||||
IL4 Signaling Pathway | |||||
Leptin Signaling Pathway | |||||
PANTHER Pathway | Axon guidance mediated by Slit/Robo | ||||
Inflammation mediated by chemokine and cytokine signaling pathway | |||||
Pathway Interaction Database | S1P3 pathway | ||||
CXCR4-mediated signaling events | |||||
Syndecan-4-mediated signaling events | |||||
HIF-1-alpha transcription factor network | |||||
Ephrin B reverse signaling | |||||
Reactome | Binding and entry of HIV virion | ||||
Chemokine receptors bind chemokines | |||||
G alpha (i) signalling events | |||||
WikiPathways | GPCRs, Class A Rhodopsin-like | ||||
Hematopoietic Stem Cell Differentiation | |||||
HIV Life Cycle | |||||
Cardiac Progenitor Differentiation | |||||
Peptide GPCRs | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
Ref 521607 | ClinicalTrials.gov (NCT00089466) Safety and Activity of the Oral HIV Entry Inhibitor AMD11070 in HIV Infected Patients. U.S. National Institutes of Health. | ||||
Ref 522865 | ClinicalTrials.gov (NCT01018979) Safety and PK/PD of TG-0054 in Multiple Myeloma, Non-Hodgkin Lymphoma and Hodgkin Disease Patients. U.S. National Institutes of Health. | ||||
Ref 523007 | ClinicalTrials.gov (NCT01105403) Exploratory Study on POL6326 in Stem Cell Mobilization. U.S. National Institutes of Health. | ||||
Ref 523067 | ClinicalTrials.gov (NCT01139788) A Study of LY2624587 in Patients With Advanced Cancer. U.S. National Institutes of Health. | ||||
Ref 523519 | ClinicalTrials.gov (NCT01374503) First in Man Study of ALX-0651, a Nanobody Inhibiting CXCR4. U.S. National Institutes of Health. | ||||
Ref 525014 | ClinicalTrials.gov (NCT02305563) Phase 1 Study of BMS-936564. U.S. National Institutes of Health. | ||||
Ref 525271 | ClinicalTrials.gov (NCT02502968) BL-8040 Addition to Consolidation Therapy in AML Patients. | ||||
Ref 530179 | A CXCR4 antagonist CTCE-9908 inhibits primary tumor growth and metastasis of breast cancer. J Surg Res. 2009 Aug;155(2):231-6. | ||||
Ref 543136 | (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: 844). | ||||
Ref 543204 | (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: 8580). | ||||
Ref 545728 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004409) | ||||
Ref 546869 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010770) | ||||
Ref 547903 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020279) | ||||
Ref 523067 | ClinicalTrials.gov (NCT01139788) A Study of LY2624587 in Patients With Advanced Cancer. U.S. National Institutes of Health. | ||||
Ref 526483 | Suradista NSC 651016 inhibits the angiogenic activity of CXCL12-stromal cell-derived factor 1alpha. Clin Cancer Res. 2002 Dec;8(12):3955-60. | ||||
Ref 527153 | Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6. Epub 2004 Jul 28.Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. | ||||
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 529115 | J Med Chem. 2007 Nov 15;50(23):5655-64. Epub 2007 Oct 24.Discovery of small molecule CXCR4 antagonists. | ||||
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. | ||||
Ref 529840 | Orally bioavailable isothioureas block function of the chemokine receptor CXCR4 in vitro and in vivo. J Med Chem. 2008 Dec 25;51(24):7915-20. | ||||
Ref 530179 | A CXCR4 antagonist CTCE-9908 inhibits primary tumor growth and metastasis of breast cancer. J Surg Res. 2009 Aug;155(2):231-6. | ||||
Ref 531347 | Beneficial effect of a CXCR4 agonist in murine models of systemic inflammation. Inflammation. 2012 Feb;35(1):130-7. | ||||
Ref 531821 | CXCR4 inhibitors: tumor vasculature and therapeutic challenges. Recent Pat Anticancer Drug Discov. 2012 Sep;7(3):251-64. | ||||
Ref 532141 | BMS-936564/MDX-1338: a fully human anti-CXCR4 antibody induces apoptosis in vitro and shows antitumor activity in vivo in hematologic malignancies. Clin Cancer Res. 2013 Jan 15;19(2):357-66. | ||||
Ref 532779 | CXCR4 Antagonist TG-0054 Mobilizes Mesenchymal Stem Cells, Attenuates Inflammation, and Preserves Cardiac Systolic Function in a Porcine Model of Myocardial Infarction. Cell Transplant. 2015;24(7):1313-28. | ||||
Ref 534456 | A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science. 1997 Sep 12;277(5332):1656-9. | ||||
Ref 534819 | A low-molecular-weight inhibitor against the chemokine receptor CXCR4: a strong anti-HIV peptide T140. Biochem Biophys Res Commun. 1998 Dec 30;253(3):877-82. | ||||
Ref 535860 | Comparative evaluation of CC chemokine-induced migration of murine CD8alpha+ and CD8alpha- dendritic cells and their in vivo trafficking. J Leukoc Biol. 2004 Feb;75(2):275-85. Epub 2003 Nov 3. | ||||
Ref 536630 | Effect of low-dose ritonavir on the pharmacokinetics of the CXCR4 antagonist AMD070 in healthy volunteers. Antimicrob Agents Chemother. 2008 May;52(5):1630-4. Epub 2008 Feb 19. | ||||
Ref 536663 | Pharmacokinetic effect of AMD070, an Oral CXCR4 antagonist, on CYP3A4 and CYP2D6 substrates midazolam and dextromethorphan in healthy volunteers. J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):559-65. | ||||
Ref 543930 | (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: 71). | ||||
Ref 544156 | Therapeutic antibodies directed at G protein-coupled receptors. MAbs. 2010 Nov-Dec; 2(6): 594-606. |
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