Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUCJY4N)

• DOT Name: C-C motif chemokine 20 (CCL20)
• Synonyms: Beta-chemokine exodus-1; CC chemokine LARC; Liver and activation-regulated chemokine; Macrophage inflammatory protein 3 alpha; MIP-3-alpha; Small-inducible cytokine A20
• Gene Name: CCL20
• UniProt ID: CCL20_HUMAN
• PDB ID: 1M8A; 2HCI; 2JYO; 5UR7; 6WWZ; 7T1E
• Pfam ID: PF00048
• Sequence:
  MCCTKSLLLAALMSVLLLHLCGESEAASNFDCCLGYTDRILHPKFIVGFTRQLANEGCDI
  NAIIFHTKKKLSVCANPKQTWVKYIVRLLSKKVKNM
• Function: Acts as a ligand for C-C chemokine receptor CCR6. Signals through binding and activation of CCR6 and induces a strong chemotactic response and mobilization of intracellular calcium ions. The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCL20 acts as a chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes. Involved in the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for optimal migration of thymic natural regulatory T cells (nTregs) and DN1 early thymocyte progenitor cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. Positively regulates sperm motility and chemotaxis via its binding to CCR6 which triggers Ca2+ mobilization in the sperm which is important for its motility. Inhibits proliferation of myeloid progenitors in colony formation assays. May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. Possesses antibacterial activity towards E.coli ATCC 25922 and S.aureus ATCC 29213.
• Tissue Specificity: Expressed in the seminal plasma, endometrial fluid and follicular fluid (at protein level). Expressed predominantly in the liver, lymph nodes, appendix, peripheral blood lymphocytes, and fetal lung. Low levels seen in thymus, prostate, testis, small intestine and colon.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  IL-17 sig.ling pathway (hsa04657)
  TNF sig.ling pathway (hsa04668)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Interleukin-10 signaling (R-HSA-6783783)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of C-C motif chemokine 20 (CCL20).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of C-C motif chemokine 20 (CCL20).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C motif chemokine 20 (CCL20).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of C-C motif chemokine 20 (CCL20).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of C-C motif chemokine 20 (CCL20).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-C motif chemokine 20 (CCL20).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of C-C motif chemokine 20 (CCL20).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of C-C motif chemokine 20 (CCL20).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of C-C motif chemokine 20 (CCL20).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of C-C motif chemokine 20 (CCL20).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of C-C motif chemokine 20 (CCL20).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C-C motif chemokine 20 (CCL20).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of C-C motif chemokine 20 (CCL20).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of C-C motif chemokine 20 (CCL20).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of C-C motif chemokine 20 (CCL20).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of C-C motif chemokine 20 (CCL20).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of C-C motif chemokine 20 (CCL20).	[16]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of C-C motif chemokine 20 (CCL20).	[17]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of C-C motif chemokine 20 (CCL20).	[18]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of C-C motif chemokine 20 (CCL20).	[12]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of C-C motif chemokine 20 (CCL20).	[12]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of C-C motif chemokine 20 (CCL20).	[19]
Malathion	DMXZ84M	Approved	Malathion increases the expression of C-C motif chemokine 20 (CCL20).	[20]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of C-C motif chemokine 20 (CCL20).	[21]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of C-C motif chemokine 20 (CCL20).	[22]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of C-C motif chemokine 20 (CCL20).	[23]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of C-C motif chemokine 20 (CCL20).	[12]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of C-C motif chemokine 20 (CCL20).	[24]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of C-C motif chemokine 20 (CCL20).	[12]
Glutathione	DMAHMT9	Approved	Glutathione decreases the expression of C-C motif chemokine 20 (CCL20).	[25]
Nicotinamide	DMUPE07	Approved	Nicotinamide increases the expression of C-C motif chemokine 20 (CCL20).	[25]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of C-C motif chemokine 20 (CCL20).	[26]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of C-C motif chemokine 20 (CCL20).	[27]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the expression of C-C motif chemokine 20 (CCL20).	[27]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of C-C motif chemokine 20 (CCL20).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of C-C motif chemokine 20 (CCL20).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-C motif chemokine 20 (CCL20).	[29]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of C-C motif chemokine 20 (CCL20).	[30]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of C-C motif chemokine 20 (CCL20).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of C-C motif chemokine 20 (CCL20).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of C-C motif chemokine 20 (CCL20).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of C-C motif chemokine 20 (CCL20).	[32]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of C-C motif chemokine 20 (CCL20).	[33]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of C-C motif chemokine 20 (CCL20).	[34]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of C-C motif chemokine 20 (CCL20).	[35]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of C-C motif chemokine 20 (CCL20).	[36]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of C-C motif chemokine 20 (CCL20).	[19]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of C-C motif chemokine 20 (CCL20).	[27]
Beta-D-Glucose	DM5IHYP	Investigative	Beta-D-Glucose increases the expression of C-C motif chemokine 20 (CCL20).	[37]

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