Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6B8P25)

• DOT Name: C-C motif chemokine 4 (CCL4)
• Synonyms: G-26 T-lymphocyte-secreted protein; HC21; Lymphocyte activation gene 1 protein; LAG-1; MIP-1-beta(1-69); Macrophage inflammatory protein 1-beta; MIP-1-beta; PAT 744; Protein H400; SIS-gamma; Small-inducible cytokine A4; T-cell activation protein 2; ACT-2
• Gene Name: CCL4
• Related Disease:
  Hepatitis
  Acute liver failure
  Allergy
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  B-cell neoplasm
  Brain ischaemia
  Breast cancer
  Colorectal carcinoma
  Dementia
  Depression
  Escherichia coli infection
  Fatty liver disease
  Glioblastoma multiforme
  Hepatitis A virus infection
  Hepatocellular carcinoma
  HIV infectious disease
  Liver cirrhosis
  Liver failure
  Lung cancer
  Lung carcinoma
  Neoplasm
  Obesity
  Pneumonia
  Pneumonitis
  Polyomavirus infection
  Psoriasis
  Pulmonary tuberculosis
  Rheumatoid arthritis
  Skin disease
  Small lymphocytic lymphoma
  Tuberculosis
  Type-1 diabetes
  Adult lymphoma
  Breast carcinoma
  Glomerulonephritis
  Hepatitis B virus infection
  Lymphoma
  Pediatric lymphoma
  Pulmonary fibrosis
  Advanced cancer
  Malaria
  Myocardial ischemia
  Plasma cell myeloma
  Status epilepticus seizure
  Type-1/2 diabetes
• UniProt ID: CCL4_HUMAN
• PDB ID: 1HUM; 1HUN; 1JE4; 2FFK; 2FIN; 2X6L; 3TN2; 4RAL
• Pfam ID: PF00048
• Sequence:
  MKLCVTVLSLLMLVAAFCSPALSAPMGSDPPTACCFSYTARKLPRNFVVDYYETSSLCSQ
  PAVVFQTKRSKQVCADPSESWVQEYVYDLELN
• Function: Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  NF-kappa B sig.ling pathway (hsa04064)
  Toll-like receptor sig.ling pathway (hsa04620)
  Cytosolic D.-sensing pathway (hsa04623)
  Human cytomegalovirus infection (hsa05163)
• 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

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis	DISXXX35	Definitive	Biomarker	[1]
Acute liver failure	DIS5EZKX	Strong	Posttranslational Modification	[2]
Allergy	DIS48ZAP	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[6]
Brain ischaemia	DIS9Q4RT	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Dementia	DISXL1WY	Strong	Biomarker	[10]
Depression	DIS3XJ69	Strong	Biomarker	[11]
Escherichia coli infection	DISPP65M	Strong	Biomarker	[12]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[14]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
HIV infectious disease	DISO97HC	Strong	Biomarker	[17]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[18]
Liver failure	DISLGEL6	Strong	Biomarker	[19]
Lung cancer	DISCM4YA	Strong	Altered Expression	[20]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Altered Expression	[21]
Obesity	DIS47Y1K	Strong	Genetic Variation	[22]
Pneumonia	DIS8EF3M	Strong	Biomarker	[3]
Pneumonitis	DIS88E0K	Strong	Biomarker	[3]
Polyomavirus infection	DISB8YKA	Strong	Biomarker	[23]
Psoriasis	DIS59VMN	Strong	Biomarker	[24]
Pulmonary tuberculosis	DIS6FLUM	Strong	Altered Expression	[25]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[26]
Skin disease	DISDW8R6	Strong	Biomarker	[27]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[28]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[29]
Type-1 diabetes	DIS7HLUB	Strong	Altered Expression	[22]
Adult lymphoma	DISK8IZR	moderate	Altered Expression	[30]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[31]
Glomerulonephritis	DISPZIQ3	moderate	Biomarker	[32]
Hepatitis B virus infection	DISLQ2XY	moderate	Biomarker	[33]
Lymphoma	DISN6V4S	moderate	Altered Expression	[30]
Pediatric lymphoma	DIS51BK2	moderate	Altered Expression	[30]
Pulmonary fibrosis	DISQKVLA	moderate	Biomarker	[34]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[35]
Malaria	DISQ9Y50	Limited	Biomarker	[36]
Myocardial ischemia	DISFTVXF	Limited	Genetic Variation	[37]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[38]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[39]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[40]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	C-C motif chemokine 4 (CCL4) decreases the response to substance of Methotrexate.	[66]

45 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 C-C motif chemokine 4 (CCL4).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of C-C motif chemokine 4 (CCL4).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C motif chemokine 4 (CCL4).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-C motif chemokine 4 (CCL4).	[44]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of C-C motif chemokine 4 (CCL4).	[27]
Marinol	DM70IK5	Approved	Marinol increases the expression of C-C motif chemokine 4 (CCL4).	[46]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of C-C motif chemokine 4 (CCL4).	[47]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of C-C motif chemokine 4 (CCL4).	[48]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of C-C motif chemokine 4 (CCL4).	[49]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of C-C motif chemokine 4 (CCL4).	[50]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of C-C motif chemokine 4 (CCL4).	[51]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of C-C motif chemokine 4 (CCL4).	[52]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of C-C motif chemokine 4 (CCL4).	[52]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of C-C motif chemokine 4 (CCL4).	[53]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of C-C motif chemokine 4 (CCL4).	[54]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone decreases the expression of C-C motif chemokine 4 (CCL4).	[55]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of C-C motif chemokine 4 (CCL4).	[56]
Budesonide	DMJIBAW	Approved	Budesonide increases the expression of C-C motif chemokine 4 (CCL4).	[52]
Clopidogrel	DMOL54H	Approved	Clopidogrel increases the expression of C-C motif chemokine 4 (CCL4).	[57]
Emetine	DMCT2YF	Approved	Emetine decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Digoxin	DMQCTIH	Approved	Digoxin decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Fludrocortisone	DMUDIR8	Approved	Fludrocortisone increases the expression of C-C motif chemokine 4 (CCL4).	[52]
Betamethasone	DMAHJEF	Approved	Betamethasone increases the expression of C-C motif chemokine 4 (CCL4).	[52]
Oxytetracycline	DMOVH1M	Approved	Oxytetracycline decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Meclocycline	DMSFQ8I	Approved	Meclocycline decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Benzocaine	DMI18HW	Approved	Benzocaine increases the expression of C-C motif chemokine 4 (CCL4).	[58]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate increases the expression of C-C motif chemokine 4 (CCL4).	[52]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of C-C motif chemokine 4 (CCL4).	[43]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of C-C motif chemokine 4 (CCL4).	[59]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of C-C motif chemokine 4 (CCL4).	[60]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of C-C motif chemokine 4 (CCL4).	[61]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of C-C motif chemokine 4 (CCL4).	[60]
Puromycin	DMDKLB5	Preclinical	Puromycin decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Cephaeline	DM1ZFCS	Preclinical	Cephaeline decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of C-C motif chemokine 4 (CCL4).	[58]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of C-C motif chemokine 4 (CCL4).	[64]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of C-C motif chemokine 4 (CCL4).	[49]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of C-C motif chemokine 4 (CCL4).	[65]
Catechol	DML0YEK	Investigative	Catechol increases the expression of C-C motif chemokine 4 (CCL4).	[49]
PALMATINE	DMJCOKV	Investigative	PALMATINE decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
7alpha-hydroxycholesterol	DMH6LD0	Investigative	7alpha-hydroxycholesterol increases the expression of C-C motif chemokine 4 (CCL4).	[65]
Propidium	DMZ1FRS	Investigative	Propidium decreases the expression of C-C motif chemokine 4 (CCL4).	[52]
Digitoxigenin	DM5AOFW	Investigative	Digitoxigenin decreases the expression of C-C motif chemokine 4 (CCL4).	[52]

1 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 C-C motif chemokine 4 (CCL4).	[62]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
geraniol	DMS3CBD	Investigative	geraniol increases the secretion of C-C motif chemokine 4 (CCL4).	[63]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the secretion of C-C motif chemokine 4 (CCL4).	[63]
Farnesol	DMV2X1B	Investigative	Farnesol increases the secretion of C-C motif chemokine 4 (CCL4).	[63]

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