CXCL12α

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Ligands
CXCL12α (Human)

GtoPdb Ligand ID: 4358

Synonyms: CXCL12 α | SDF-1α | stromal cell-derived factor-1α

Compound class: Endogenous peptide in human, mouse or rat

Comment: CXCL12-1α and β were the first isoforms of this chemokine identified. Both proteins contain a signal peptide sequence that mediates their secretion via the canonical intracellular secretory pathway. CXCL12 participates in a variety of processes central to homeostasis and physiology, exerting its biological effects by binding to the chemokine receptors CXCR4 and CXCR7.

Species: Human

View interactive charts of activity data across species

References
1. Adlere I, Sun S, Zarca A, Roumen L, Gozelle M, Viciano CP, Caspar B, Arimont M, Bebelman JP, Briddon SJ et al.. (2019) Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists. Eur J Med Chem, 162: 631-649. DOI: 10.1016/j.ejmech.2018.10.060 [PMID:30476826]
2. Gravel S, Malouf C, Boulais PE, Berchiche YA, Oishi S, Fujii N, Leduc R, Sinnett D, Heveker N. (2010) The peptidomimetic CXCR4 antagonist TC14012 recruits beta-arrestin to CXCR7: roles of receptor domains. J Biol Chem, 285 (49): 37939-43. [PMID:20956518]
3. Hesselgesser J, Liang M, Hoxie J, Greenberg M, Brass LF, Orsini MJ, Taub D, Horuk R. (1998) Identification and characterization of the CXCR4 chemokine receptor in human T cell lines: ligand binding, biological activity, and HIV-1 infectivity. J Immunol, 160 (2): 877-83. [PMID:9551924]
4. Hoellenriegel J, Zboralski D, Maasch C, Rosin NY, Wierda WG, Keating MJ, Kruschinski A, Burger JA. (2014) The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization. Blood, 123 (7): 1032-9. [PMID:24277076]
5. Krikun G. (2018) The CXL12/CXCR4/CXCR7 axis in female reproductive tract disease: Review. Am J Reprod Immunol, 80 (5): e13028. [PMID:30106199]
6. Loetscher P, Gong JH, Dewald B, Baggiolini M, Clark-Lewis I. (1998) N-terminal peptides of stromal cell-derived factor-1 with CXC chemokine receptor 4 agonist and antagonist activities. J Biol Chem, 273 (35): 22279-83. [PMID:9712844]
7. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T. (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature, 382 (6592): 635-8. [PMID:8757135]
8. Nguyen HH, Kim MB, Wilson RJ, Butch CJ, Kuo KM, Miller EJ, Tahirovic YA, Jecs E, Truax VM, Wang T et al.. (2018) Design, Synthesis, and Pharmacological Evaluation of Second-Generation Tetrahydroisoquinoline-Based CXCR4 Antagonists with Favorable ADME Properties. J Med Chem, 61 (16): 7168-7188. [PMID:30052039]
9. Patrussi L, Baldari CT. (2011) The CXCL12/CXCR4 axis as a therapeutic target in cancer and HIV-1 infection. Curr Med Chem, 18 (4): 497-512. [PMID:21143114]
10. Ray P, Stacer AC, Fenner J, Cavnar SP, Meguiar K, Brown M, Luker KE, Luker GD. (2015) CXCL12-γ in primary tumors drives breast cancer metastasis. Oncogene, 34 (16): 2043-51. [PMID:24909174]
11. Regenass P, Abboud D, Daubeuf F, Lehalle C, Gizzi P, Riché S, Hachet-Haas M, Rohmer F, Gasparik V, Boeglin D et al.. (2018) Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia. J Med Chem, 61 (17): 7671-7686. [PMID:30106292]
12. Sierro F, Biben C, Martínez-Muñoz L, Mellado M, Ransohoff RM, Li M, Woehl B, Leung H, Groom J, Batten M, Harvey RP, Martínez-A C, Mackay CR, Mackay F. (2007) Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc Natl Acad Sci USA, 104 (37): 14759-64. [PMID:17804806]
13. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen, 18 (5): 599-609. [PMID:23396314]
14. Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y, Kitamura Y, Matsushima K, Yoshida N, Nishikawa S et al.. (1998) The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature, 393 (6685): 591-4. [PMID:9634237]
15. Wang C, Chen W, Shen J. (2018) CXCR7 Targeting and Its Major Disease Relevance. Front Pharmacol, 9: 641. [PMID:29977203]
16. Weng Y, Siciliano SJ, Waldburger KE, Sirotina-Meisher A, Staruch MJ, Daugherty BL, Gould SL, Springer MS, DeMartino JA. (1998) Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors. J Biol Chem, 273 (29): 18288-91. [PMID:9660793]
17. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. (1998) Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature, 393 (6685): 595-9. [PMID:9634238]

References

1. Adlere I, Sun S, Zarca A, Roumen L, Gozelle M, Viciano CP, Caspar B, Arimont M, Bebelman JP, Briddon SJ et al.. (2019)
Structure-based exploration and pharmacological evaluation of N-substituted piperidin-4-yl-methanamine CXCR4 chemokine receptor antagonists.
Eur J Med Chem, 162: 631-649. DOI: 10.1016/j.ejmech.2018.10.060 [PMID:30476826]

2. Gravel S, Malouf C, Boulais PE, Berchiche YA, Oishi S, Fujii N, Leduc R, Sinnett D, Heveker N. (2010)
The peptidomimetic CXCR4 antagonist TC14012 recruits beta-arrestin to CXCR7: roles of receptor domains.
J Biol Chem, 285 (49): 37939-43. [PMID:20956518]

3. Hesselgesser J, Liang M, Hoxie J, Greenberg M, Brass LF, Orsini MJ, Taub D, Horuk R. (1998)
Identification and characterization of the CXCR4 chemokine receptor in human T cell lines: ligand binding, biological activity, and HIV-1 infectivity.
J Immunol, 160 (2): 877-83. [PMID:9551924]

4. Hoellenriegel J, Zboralski D, Maasch C, Rosin NY, Wierda WG, Keating MJ, Kruschinski A, Burger JA. (2014)
The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization.
Blood, 123 (7): 1032-9. [PMID:24277076]

5. Krikun G. (2018)
The CXL12/CXCR4/CXCR7 axis in female reproductive tract disease: Review.
Am J Reprod Immunol, 80 (5): e13028. [PMID:30106199]

6. Loetscher P, Gong JH, Dewald B, Baggiolini M, Clark-Lewis I. (1998)
N-terminal peptides of stromal cell-derived factor-1 with CXC chemokine receptor 4 agonist and antagonist activities.
J Biol Chem, 273 (35): 22279-83. [PMID:9712844]

7. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T. (1996)
Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1.
Nature, 382 (6592): 635-8. [PMID:8757135]

8. Nguyen HH, Kim MB, Wilson RJ, Butch CJ, Kuo KM, Miller EJ, Tahirovic YA, Jecs E, Truax VM, Wang T et al.. (2018)
Design, Synthesis, and Pharmacological Evaluation of Second-Generation Tetrahydroisoquinoline-Based CXCR4 Antagonists with Favorable ADME Properties.
J Med Chem, 61 (16): 7168-7188. [PMID:30052039]

9. Patrussi L, Baldari CT. (2011)
The CXCL12/CXCR4 axis as a therapeutic target in cancer and HIV-1 infection.
Curr Med Chem, 18 (4): 497-512. [PMID:21143114]

10. Ray P, Stacer AC, Fenner J, Cavnar SP, Meguiar K, Brown M, Luker KE, Luker GD. (2015)
CXCL12-γ in primary tumors drives breast cancer metastasis.
Oncogene, 34 (16): 2043-51. [PMID:24909174]

11. Regenass P, Abboud D, Daubeuf F, Lehalle C, Gizzi P, Riché S, Hachet-Haas M, Rohmer F, Gasparik V, Boeglin D et al.. (2018)
Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia.
J Med Chem, 61 (17): 7671-7686. [PMID:30106292]

12. Sierro F, Biben C, Martínez-Muñoz L, Mellado M, Ransohoff RM, Li M, Woehl B, Leung H, Groom J, Batten M, Harvey RP, Martínez-A C, Mackay CR, Mackay F. (2007)
Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7.
Proc Natl Acad Sci USA, 104 (37): 14759-64. [PMID:17804806]

13. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013)
Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors.
J Biomol Screen, 18 (5): 599-609. [PMID:23396314]

14. Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y, Kitamura Y, Matsushima K, Yoshida N, Nishikawa S et al.. (1998)
The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract.
Nature, 393 (6685): 591-4. [PMID:9634237]

15. Wang C, Chen W, Shen J. (2018)
CXCR7 Targeting and Its Major Disease Relevance.
Front Pharmacol, 9: 641. [PMID:29977203]

16. Weng Y, Siciliano SJ, Waldburger KE, Sirotina-Meisher A, Staruch MJ, Daugherty BL, Gould SL, Springer MS, DeMartino JA. (1998)
Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors.
J Biol Chem, 273 (29): 18288-91. [PMID:9660793]

17. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. (1998)
Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development.
Nature, 393 (6685): 595-9. [PMID:9634238]

CXCL12α

GtoPdb Ligand ID: 4358

Ligand Activity Visualisation Charts