Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT9DWLC)

• DTT Name: T-cell-specific protein RANTES (CCL5)
• Synonyms: Tcellspecific protein RANTES; TCP228; T cellspecific protein P228; T cell-specific protein P228; Smallinducible cytokine A5; Small-inducible cytokine A5; SISdelta; SIS-delta; SCYA5; RANTES(468); Eosinophil chemotactic cytokine; EoCP; D17S136E; CC motif chemokine 5; C-C motif chemokine 5
• Gene Name: CCL5
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: CC chemokine
• UniProt ID: CCL5_HUMAN
• TTD ID: T16263
• Sequence:
  MKVSAAALAVILIATALCAPASASPYSSDTTPCCFAYIARPLPRAHIKEYFYTSGKCSNP
  AVVFVTRKNRQVCANPEKKWVREYINSLEMS
• Function: Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils. May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells. Chemoattractant for blood monocytes, memory T-helper cells and eosinophils.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine signaling pathway (hsa04062)
  Toll-like receptor signaling pathway (hsa04620)
  NOD-like receptor signaling pathway (hsa04621)
  Cytosolic DNA-sensing pathway (hsa04623)
  TNF signaling pathway (hsa04668)
  Prion diseases (hsa05020)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Influenza A (hsa05164)
  Herpes simplex infection (hsa05168)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NI-0701	DM32VKQ	Autoimmune diabetes	5A10	Phase 1	[1]

References

• [1] Handbook of Therapeutic Antibodies. Stefan D bel, Janice M. Reichert, 2014. Page(1021).