Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4UGTF)

• DTT Name: Stromal cell-derived factor 1 (CXCL12)
• Synonyms: hSDF-1; SDF1B; SDF1A; SDF1; SDF-1; Pre-B cell growth-stimulating factor; Pre-B cell growth stimulating factor; PBSF; Intercrine reduced in hepatomas; IRH; HIRH; C-X-C motif chemokine 12
• Gene Name: CXCL12
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: CXC chemokine
• UniProt ID: SDF1_HUMAN
• TTD ID: T04773
• Sequence:
  MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIV
  ARLKNNNRQVCIDPKLKWIQEYLEKALNKRFKM
• Function: Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells. Chemoattractant active on T-lymphocytes and monocytes but not neutrophils.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine signaling pathway (hsa04062)
  NF-kappa B signaling pathway (hsa04064)
  Axon guidance (hsa04360)
  Leukocyte transendothelial migration (hsa04670)
  Intestinal immune network for IgA production (hsa04672)
  Pathways in cancer (hsa05200)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  Chemokine receptors bind chemokines (R-HSA-380108)
  G alpha (i) signalling events (R-HSA-418594)
  Nuclear signaling by ERBB4 (R-HSA-1251985)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dociparstat sodium	DMQLSMB	Acute myeloid leukaemia	2A60	Phase 3	[2]
MyoCell SDF-1	DMS9GE1	Heart failure	BD10-BD13	Phase 3	[1]
SDF-1	DM80HOV	Heart failure	BD10-BD13	Phase 2	[3]
NOX-A12	DMMKN4Q	Macular degeneration	9B78.3	Phase 1	[4]
REC-02	DMHT5XV	Congestive heart failure	BD10	Phase 1	[5]

References

• [1] Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine. Expert Opin Biol Ther. 2011 Feb;11(2):189-97.
• [2] Clinical pipeline report, company report or official report of Chimerix.
• [3] SDF-1 in myocardial repair. Gene Ther. 2012 Jun;19(6):583-7.
• [4] SDF-1/CXCR4/CXCR7 is pivotal for vascular smooth muscle cell proliferation and chronic allograft vasculopathy. Transpl Int. 2015 Dec;28(12):1426-35.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)