Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPLGI0E)

• DOT Name: Fractalkine (CX3CL1)
• Synonyms: C-X3-C motif chemokine 1; CX3C membrane-anchored chemokine; Neurotactin; Small-inducible cytokine D1
• Gene Name: CX3CL1
• UniProt ID: X3CL1_HUMAN
• PDB ID: 1B2T; 1F2L; 3ONA; 4XT1; 4XT3; 5WB2; 7RKF; 7RKM; 7RKN; 7XBX
• Pfam ID: PF00048
• Sequence:
  MAPISLSWLLRLATFCHLTVLLAGQHHGVTKCNITCSKMTSKIPVALLIHYQQNQASCGK
  RAIILETRQHRLFCADPKEQWVKDAMQHLDRQAAALTRNGGTFEKQIGEVKPRTTPAAGG
  MDESVVLEPEATGESSSLEPTPSSQEAQRALGTSPELPTGVTGSSGTRLPPTPKAQDGGP
  VGTELFRVPPVSTAATWQSSAPHQPGPSLWAEAKTSEAPSTQDPSTQASTASSPAPEENA
  PSEGQRVWGQGQSPRPENSLEREEMGPVPAHTDAFQDWGPGSMAHVSVVPVSSEGTPSRE
  PVASGSWTPKAEEPIHATMDPQRLGVLITPVPDAQAATRRQAVGLLAFLGLLFCLGVAMF
  TYQSLQGCPRKMAGEMAEGLRYIPRSCGSNSYVLVPV
• Function: Chemokine that acts as a ligand for both CX3CR1 and integrins ITGAV:ITGB3 and ITGA4:ITGB1. The CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune response, inflammation, cell adhesion and chemotaxis. Regulates leukocyte adhesion and migration processes at the endothelium. Can activate integrins in both a CX3CR1-dependent and CX3CR1-independent manner. In the presence of CX3CR1, activates integrins by binding to the classical ligand-binding site (site 1) in integrins. In the absence of CX3CR1, binds to a second site (site 2) in integrins which is distinct from site 1 and enhances the binding of other integrin ligands to site 1 ; [Processed fractalkine]: The soluble form is chemotactic for T-cells and monocytes, but not for neutrophils; [Fractalkine]: The membrane-bound form promotes adhesion of those leukocytes to endothelial cells; (Microbial infection) Mediates the cytoadherence of erythrocytes infected with parasite P.falciparum (strain 3D7) with endothelial cells by interacting with P.falciparum CBP1 and CBP2 expressed at the surface of erythrocytes. The adhesion prevents the elimination of infected erythrocytes by the spleen (Probable).
• Tissue Specificity: Expressed in the seminal plasma, endometrial fluid and follicular fluid (at protein level). Small intestine, colon, testis, prostate, heart, brain, lung, skeletal muscle, kidney and pancreas. Most abundant in the brain and heart.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Efferocytosis (hsa04148)
  TNF sig.ling pathway (hsa04668)
  Human cytomegalovirus infection (hsa05163)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fractalkine (CX3CL1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fractalkine (CX3CL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fractalkine (CX3CL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Fractalkine (CX3CL1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fractalkine (CX3CL1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fractalkine (CX3CL1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fractalkine (CX3CL1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fractalkine (CX3CL1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Fractalkine (CX3CL1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Fractalkine (CX3CL1).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Fractalkine (CX3CL1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fractalkine (CX3CL1).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Fractalkine (CX3CL1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Fractalkine (CX3CL1).	[14]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Fractalkine (CX3CL1).	[16]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Fractalkine (CX3CL1).	[17]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Fractalkine (CX3CL1).	[17]
Fructose	DM43AN2	Approved	Fructose increases the expression of Fractalkine (CX3CL1).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Fractalkine (CX3CL1).	[19]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Fractalkine (CX3CL1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fractalkine (CX3CL1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Fractalkine (CX3CL1).	[23]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Fractalkine (CX3CL1).	[24]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Fractalkine (CX3CL1).	[25]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the localization of Fractalkine (CX3CL1).	[15]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fractalkine (CX3CL1).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Fractalkine (CX3CL1).	[22]

References

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