Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSCA5CK)

• DOT Name: C-C motif chemokine 5 (CCL5)
• Synonyms: EoCP; Eosinophil chemotactic cytokine; SIS-delta; Small-inducible cytokine A5; T cell-specific protein P228; TCP228; T-cell-specific protein RANTES
• Gene Name: CCL5
• UniProt ID: CCL5_HUMAN
• PDB ID: 1B3A; 1EQT; 1HRJ; 1RTN; 1RTO; 1U4L; 1U4M; 1U4P; 1U4R; 2L9H; 2VXW; 5CMD; 5COY; 5DNF; 5L2U; 5UIW; 6AEZ; 6C6D; 6FGP; 6LOG; 6STK; 7F1R; 7O7F
• Pfam ID: PF00048
• Sequence:
  MKVSAAALAVILIATALCAPASASPYSSDTTPCCFAYIARPLPRAHIKEYFYTSGKCSNP
  AVVFVTRKNRQVCANPEKKWVREYINSLEMS
• Function: Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. 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). 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.
• Tissue Specificity: Expressed in the follicular fluid (at protein level). T-cell and macrophage specific.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  Cytosolic D.-sensing pathway (hsa04623)
  TNF sig.ling pathway (hsa04668)
  Prion disease (hsa05020)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Shigellosis (hsa05131)
  Chagas disease (hsa05142)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
• 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C motif chemokine 5 (CCL5).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of C-C motif chemokine 5 (CCL5).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of C-C motif chemokine 5 (CCL5).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of C-C motif chemokine 5 (CCL5).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of C-C motif chemokine 5 (CCL5).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C-C motif chemokine 5 (CCL5).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of C-C motif chemokine 5 (CCL5).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of C-C motif chemokine 5 (CCL5).	[10]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of C-C motif chemokine 5 (CCL5).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of C-C motif chemokine 5 (CCL5).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of C-C motif chemokine 5 (CCL5).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of C-C motif chemokine 5 (CCL5).	[14]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of C-C motif chemokine 5 (CCL5).	[15]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of C-C motif chemokine 5 (CCL5).	[18]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of C-C motif chemokine 5 (CCL5).	[19]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of C-C motif chemokine 5 (CCL5).	[20]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of C-C motif chemokine 5 (CCL5).	[21]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of C-C motif chemokine 5 (CCL5).	[22]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of C-C motif chemokine 5 (CCL5).	[23]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of C-C motif chemokine 5 (CCL5).	[24]
Morphine	DMRMS0L	Approved	Morphine decreases the expression of C-C motif chemokine 5 (CCL5).	[26]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of C-C motif chemokine 5 (CCL5).	[27]
Clopidogrel	DMOL54H	Approved	Clopidogrel increases the expression of C-C motif chemokine 5 (CCL5).	[29]
Emetine	DMCT2YF	Approved	Emetine decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
Digoxin	DMQCTIH	Approved	Digoxin decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
Oxytetracycline	DMOVH1M	Approved	Oxytetracycline decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
Meclocycline	DMSFQ8I	Approved	Meclocycline decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the expression of C-C motif chemokine 5 (CCL5).	[31]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of C-C motif chemokine 5 (CCL5).	[1]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of C-C motif chemokine 5 (CCL5).	[32]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of C-C motif chemokine 5 (CCL5).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of C-C motif chemokine 5 (CCL5).	[36]
Cephaeline	DM1ZFCS	Preclinical	Cephaeline decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of C-C motif chemokine 5 (CCL5).	[38]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of C-C motif chemokine 5 (CCL5).	[39]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of C-C motif chemokine 5 (CCL5).	[40]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of C-C motif chemokine 5 (CCL5).	[42]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of C-C motif chemokine 5 (CCL5).	[43]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of C-C motif chemokine 5 (CCL5).	[44]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of C-C motif chemokine 5 (CCL5).	[45]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of C-C motif chemokine 5 (CCL5).	[15]
GW7604	DMCA4RM	Investigative	GW7604 increases the expression of C-C motif chemokine 5 (CCL5).	[10]
Catechol	DML0YEK	Investigative	Catechol increases the expression of C-C motif chemokine 5 (CCL5).	[15]
PALMATINE	DMJCOKV	Investigative	PALMATINE decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
ANTHRAQUINONE	DM29I0Y	Investigative	ANTHRAQUINONE increases the expression of C-C motif chemokine 5 (CCL5).	[47]
Propidium	DMZ1FRS	Investigative	Propidium decreases the expression of C-C motif chemokine 5 (CCL5).	[30]
Digitoxigenin	DM5AOFW	Investigative	Digitoxigenin decreases the expression of C-C motif chemokine 5 (CCL5).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of C-C motif chemokine 5 (CCL5).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-C motif chemokine 5 (CCL5).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the degradation of C-C motif chemokine 5 (CCL5).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the response to substance of C-C motif chemokine 5 (CCL5).	[16]
Ethanol	DMDRQZU	Approved	Ethanol increases the secretion of C-C motif chemokine 5 (CCL5).	[17]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the response to substance of C-C motif chemokine 5 (CCL5).	[16]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide decreases the secretion of C-C motif chemokine 5 (CCL5).	[25]
Norepinephrine	DMOUC09	Approved	Norepinephrine increases the secretion of C-C motif chemokine 5 (CCL5).	[28]
Telmisartan	DMS3GX2	Phase 3 Trial	Telmisartan decreases the response to substance of C-C motif chemokine 5 (CCL5).	[16]
DNCB	DMDTVYC	Phase 2	DNCB increases the secretion of C-C motif chemokine 5 (CCL5).	[34]
Arecoline	DMFJZK3	Phase 1	Arecoline increases the secretion of C-C motif chemokine 5 (CCL5).	[37]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the secretion of C-C motif chemokine 5 (CCL5).	[41]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the secretion of C-C motif chemokine 5 (CCL5).	[34]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the secretion of C-C motif chemokine 5 (CCL5).	[46]
Nitrosoglutathione	DMZ9WI4	Investigative	Nitrosoglutathione decreases the secretion of C-C motif chemokine 5 (CCL5).	[25]
GW1929	DMOV980	Investigative	GW1929 decreases the response to substance of C-C motif chemokine 5 (CCL5).	[16]

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