Details of Drug Off-Target (DOT)

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

DOT Name Interleukin-10 (IL10)
Synonyms IL-10; Cytokine synthesis inhibitory factor; CSIF
Gene Name IL10
Related Disease
Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome ( )
UniProt ID
IL10_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1ILK; 1INR; 1J7V; 1LK3; 1Y6K; 2H24; 2ILK; 6X93
Pfam ID
PF00726
Sequence
MHSSALLCCLVLLTGVRASPGQGTQSENSCTHFPGNLPNMLRDLRDAFSRVKTFFQMKDQ
LDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHVNSLGENLKTLR
LRLRRCHRFLPCENKSKAVEQVKNAFNKLQEKGIYKAMSEFDIFINYIEAYMTMKIRN
Function
Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha. Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation. In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling.
Tissue Specificity Produced by a variety of cell lines, including T-cells, macrophages, mast cells and other cell types.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
FoxO sig.ling pathway (hsa04068 )
Efferocytosis (hsa04148 )
C-type lectin receptor sig.ling pathway (hsa04625 )
JAK-STAT sig.ling pathway (hsa04630 )
T cell receptor sig.ling pathway (hsa04660 )
Intesti.l immune network for IgA production (hsa04672 )
Pertussis (hsa05133 )
Yersinia infection (hsa05135 )
Leishmaniasis (hsa05140 )
Chagas disease (hsa05142 )
African trypanosomiasis (hsa05143 )
Malaria (hsa05144 )
Toxoplasmosis (hsa05145 )
Amoebiasis (hsa05146 )
Staphylococcus aureus infection (hsa05150 )
Tuberculosis (hsa05152 )
Asthma (hsa05310 )
Autoimmune thyroid disease (hsa05320 )
Inflammatory bowel disease (hsa05321 )
Systemic lupus erythematosus (hsa05322 )
Allograft rejection (hsa05330 )
Reactome Pathway
Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 )
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505 )
CD163 mediating an anti-inflammatory response (R-HSA-9662834 )
FCGR3A-mediated IL10 synthesis (R-HSA-9664323 )
Interleukin-10 signaling (R-HSA-6783783 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome DISB2Y7L Supportive Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Aspirin DM672AH Approved Interleukin-10 (IL10) increases the response to substance of Aspirin. [67]
Diclofenac DMPIHLS Approved Interleukin-10 (IL10) increases the response to substance of Diclofenac. [68]
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This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
PGF2alpha DM4XAU7 Clinical trial Interleukin-10 (IL10) increases the abundance of PGF2alpha. [69]
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53 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 Interleukin-10 (IL10). [2]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Interleukin-10 (IL10). [3]
Quercetin DM3NC4M Approved Quercetin affects the expression of Interleukin-10 (IL10). [4]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Interleukin-10 (IL10). [5]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Interleukin-10 (IL10). [6]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Interleukin-10 (IL10). [7]
Progesterone DMUY35B Approved Progesterone increases the expression of Interleukin-10 (IL10). [8]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Interleukin-10 (IL10). [9]
Bortezomib DMNO38U Approved Bortezomib affects the expression of Interleukin-10 (IL10). [10]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Interleukin-10 (IL10). [12]
Paclitaxel DMLB81S Approved Paclitaxel increases the expression of Interleukin-10 (IL10). [13]
Nicotine DMWX5CO Approved Nicotine decreases the expression of Interleukin-10 (IL10). [14]
Simvastatin DM30SGU Approved Simvastatin increases the expression of Interleukin-10 (IL10). [17]
Gemcitabine DMSE3I7 Approved Gemcitabine decreases the expression of Interleukin-10 (IL10). [18]
Thalidomide DM70BU5 Approved Thalidomide affects the expression of Interleukin-10 (IL10). [20]
Dinoprostone DMTYOPD Approved Dinoprostone decreases the expression of Interleukin-10 (IL10). [21]
Cholecalciferol DMGU74E Approved Cholecalciferol increases the expression of Interleukin-10 (IL10). [12]
Propofol DMB4OLE Approved Propofol increases the expression of Interleukin-10 (IL10). [23]
Carvedilol DMHTEAO Approved Carvedilol increases the expression of Interleukin-10 (IL10). [25]
Reserpine DM6VM38 Approved Reserpine decreases the expression of Interleukin-10 (IL10). [27]
Ibrutinib DMHZCPO Approved Ibrutinib decreases the expression of Interleukin-10 (IL10). [29]
Paroxetine DM5PVQE Approved Paroxetine increases the expression of Interleukin-10 (IL10). [30]
Terbutaline DMD4381 Approved Terbutaline increases the expression of Interleukin-10 (IL10). [31]
Perindopril DMOPZDT Approved Perindopril increases the expression of Interleukin-10 (IL10). [32]
Bisoprolol DM3UZ95 Approved Bisoprolol increases the expression of Interleukin-10 (IL10). [32]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone decreases the expression of Interleukin-10 (IL10). [35]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate decreases the expression of Interleukin-10 (IL10). [36]
Apilimod dimesylate DM4N2O0 Phase 2 Apilimod dimesylate increases the expression of Interleukin-10 (IL10). [38]
Sodium stibogluconate DMH5MVE Phase 2 Sodium stibogluconate decreases the expression of Interleukin-10 (IL10). [39]
Bryostatin-1 DM1JOXY Phase 2 Bryostatin-1 decreases the expression of Interleukin-10 (IL10). [36]
Lipoteichoic acid DMEMRW0 Phase 1/2 Lipoteichoic acid increases the expression of Interleukin-10 (IL10). [41]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Interleukin-10 (IL10). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Interleukin-10 (IL10). [42]
Ribavirin DMEYLH9 Phase 1 Trial Ribavirin decreases the expression of Interleukin-10 (IL10). [43]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the expression of Interleukin-10 (IL10). [44]
PMID27336223-Compound-11 DMBN6KU Patented PMID27336223-Compound-11 decreases the expression of Interleukin-10 (IL10). [45]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Interleukin-10 (IL10). [46]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Interleukin-10 (IL10). [47]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Interleukin-10 (IL10). [48]
geraniol DMS3CBD Investigative geraniol increases the expression of Interleukin-10 (IL10). [49]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of Interleukin-10 (IL10). [50]
Rapamycin Immunosuppressant Drug DM678IB Investigative Rapamycin Immunosuppressant Drug decreases the expression of Interleukin-10 (IL10). [41]
Aminohippuric acid DMUN54G Investigative Aminohippuric acid decreases the expression of Interleukin-10 (IL10). [53]
Cordycepin DM72Y01 Investigative Cordycepin increases the expression of Interleukin-10 (IL10). [54]
Rutin DMEHRAJ Investigative Rutin increases the expression of Interleukin-10 (IL10). [55]
CATECHIN DMY38SB Investigative CATECHIN increases the expression of Interleukin-10 (IL10). [55]
Linoleic acid DMDGPY9 Investigative Linoleic acid increases the expression of Interleukin-10 (IL10). [57]
CYCLOPAMINE DMEM2SW Investigative CYCLOPAMINE increases the expression of Interleukin-10 (IL10). [61]
LUPEOL DM4ZLUH Investigative LUPEOL decreases the expression of Interleukin-10 (IL10). [62]
Suramin DMTOUY9 Investigative Suramin decreases the activity of Interleukin-10 (IL10). [63]
methyl isocyanate DME4JGF Investigative methyl isocyanate increases the expression of Interleukin-10 (IL10). [64]
SGC-CBP30 DMTLRGZ Investigative SGC-CBP30 decreases the expression of Interleukin-10 (IL10). [65]
CPI-203 DMXSYTA Investigative CPI-203 decreases the expression of Interleukin-10 (IL10). [66]
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⏷ Show the Full List of 53 Drug(s)
25 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Hydroquinone DM6AVR4 Approved Hydroquinone increases the secretion of Interleukin-10 (IL10). [11]
Indomethacin DMSC4A7 Approved Indomethacin decreases the secretion of Interleukin-10 (IL10). [15]
Cocaine DMSOX7I Approved Cocaine decreases the secretion of Interleukin-10 (IL10). [16]
Acetic Acid, Glacial DM4SJ5Y Approved Acetic Acid, Glacial increases the secretion of Interleukin-10 (IL10). [19]
Nitric Oxide DM1RBYG Approved Nitric Oxide decreases the secretion of Interleukin-10 (IL10). [22]
Isoniazid DM5JVS3 Approved Isoniazid increases the secretion of Interleukin-10 (IL10). [24]
Pomalidomide DMTGBAX Approved Pomalidomide increases the secretion of Interleukin-10 (IL10). [26]
Clonidine DM6RZ9Q Approved Clonidine increases the secretion of Interleukin-10 (IL10). [28]
Furosemide DMMQ8ZG Approved Furosemide decreases the secretion of Interleukin-10 (IL10). [28]
Hydralazine DMU8JGH Approved Hydralazine increases the secretion of Interleukin-10 (IL10). [28]
Diazoxide DML1538 Approved Diazoxide decreases the secretion of Interleukin-10 (IL10). [28]
Beclomethasone dipropionate DM5NW1E Phase 4 Beclomethasone dipropionate decreases the secretion of Interleukin-10 (IL10). [33]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the secretion of Interleukin-10 (IL10). [34]
MK-2206 DMT1OZ6 Phase 2 MK-2206 increases the secretion of Interleukin-10 (IL10). [37]
Resiquimod DML6XSP Phase 2 Resiquimod increases the secretion of Interleukin-10 (IL10). [40]
Ro 20-1724 DM0PSCF Terminated Ro 20-1724 decreases the secretion of Interleukin-10 (IL10). [33]
crotylaldehyde DMTWRQI Investigative crotylaldehyde decreases the secretion of Interleukin-10 (IL10). [51]
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos decreases the secretion of Interleukin-10 (IL10). [52]
acrolein DMAMCSR Investigative acrolein decreases the secretion of Interleukin-10 (IL10). [51]
Benzoquinone DMNBA0G Investigative Benzoquinone increases the secretion of Interleukin-10 (IL10). [56]
N-nonylphenol DMH3OUX Investigative N-nonylphenol increases the secretion of Interleukin-10 (IL10). [58]
Beta-D-Glucose DM5IHYP Investigative Beta-D-Glucose increases the secretion of Interleukin-10 (IL10). [59]
Syringic Acid DM802V7 Investigative Syringic Acid decreases the secretion of Interleukin-10 (IL10). [60]
Nitrosoglutathione DMZ9WI4 Investigative Nitrosoglutathione decreases the secretion of Interleukin-10 (IL10). [22]
ROLIPRAM DMJ03UM Investigative ROLIPRAM decreases the secretion of Interleukin-10 (IL10). [33]
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⏷ Show the Full List of 25 Drug(s)

References

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