Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGO5P4R)

• DOT Name: Toll-like receptor 2 (TLR2)
• Synonyms: Toll/interleukin-1 receptor-like protein 4; CD antigen CD282
• Gene Name: TLR2
• UniProt ID: TLR2_HUMAN
• PDB ID: 1FYW; 1FYX; 1O77; 2Z7X; 2Z80; 6NIG; 8AR0
• Pfam ID: PF00560 ; PF13855 ; PF01463 ; PF01582
• Sequence:
  MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLS
  NNRITYISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWF
  KPLSSLTFLNLLGNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELE
  IDASDLQSYEPKSLKSIQNVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFS
  ELSTGETNSLIKKFTFRNVKITDESLFQVMKLLNQISGLLELEFDDCTLNGVGNFRASDN
  DRVIDPGKVETLTIRRLHIPRFYLFYDLSTLYSLTERVKRITVENSKVFLVPCLLSQHLK
  SLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQNHLASLEKTGETLLTLKNLTNIDI
  SKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDVSNNNLNLFSLNLPQLK
  ELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAGGNNFICSCE
  FLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGMCCALFL
  LILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVENLMV
  QELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFS
  HFRLFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRA
  AIKS
• Function: Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6. Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4. MAPK activation in response to bacterial peptidoglycan also occurs via this receptor. Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen. M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression. Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides. Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM.
• Tissue Specificity: Highly expressed in peripheral blood leukocytes, in particular in monocytes, in bone marrow, lymph node and in spleen. Also detected in lung and in fetal liver. Levels are low in other tissues.
• KEGG Pathway:
  Phagosome (hsa04145)
  PI3K-Akt sig.ling pathway (hsa04151)
  Neutrophil extracellular trap formation (hsa04613)
  Toll-like receptor sig.ling pathway (hsa04620)
  Salmonella infection (hsa05132)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Proteoglycans in cancer (hsa05205)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Inflammatory bowel disease (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Beta defensins (R-HSA-1461957)
  MyD88 (R-HSA-166058)
  Toll Like Receptor TLR1 (R-HSA-168179)
  Toll Like Receptor TLR6 (R-HSA-168188)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  Neutrophil degranulation (R-HSA-6798695)
  Modulation by Mtb of host immune system (R-HSA-9637628)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Toll-like receptor 2 (TLR2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Toll-like receptor 2 (TLR2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Toll-like receptor 2 (TLR2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Toll-like receptor 2 (TLR2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Toll-like receptor 2 (TLR2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Toll-like receptor 2 (TLR2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Toll-like receptor 2 (TLR2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Toll-like receptor 2 (TLR2).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Toll-like receptor 2 (TLR2).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Toll-like receptor 2 (TLR2).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Toll-like receptor 2 (TLR2).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Toll-like receptor 2 (TLR2).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Toll-like receptor 2 (TLR2).	[13]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Toll-like receptor 2 (TLR2).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Toll-like receptor 2 (TLR2).	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Toll-like receptor 2 (TLR2).	[11]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Toll-like receptor 2 (TLR2).	[11]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Toll-like receptor 2 (TLR2).	[14]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Toll-like receptor 2 (TLR2).	[15]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Toll-like receptor 2 (TLR2).	[16]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Toll-like receptor 2 (TLR2).	[11]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Toll-like receptor 2 (TLR2).	[17]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Toll-like receptor 2 (TLR2).	[11]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the expression of Toll-like receptor 2 (TLR2).	[18]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Toll-like receptor 2 (TLR2).	[17]
Glutathione	DMAHMT9	Approved	Glutathione decreases the expression of Toll-like receptor 2 (TLR2).	[19]
Tibolone	DM78XFG	Approved	Tibolone increases the expression of Toll-like receptor 2 (TLR2).	[20]
Alfacalcidol	DM1237M	Phase 4	Alfacalcidol decreases the expression of Toll-like receptor 2 (TLR2).	[21]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Toll-like receptor 2 (TLR2).	[22]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Toll-like receptor 2 (TLR2).	[16]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Toll-like receptor 2 (TLR2).	[6]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Toll-like receptor 2 (TLR2).	[23]
PMID27336223-Compound-11	DMBN6KU	Patented	PMID27336223-Compound-11 decreases the expression of Toll-like receptor 2 (TLR2).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Toll-like receptor 2 (TLR2).	[26]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Toll-like receptor 2 (TLR2).	[27]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Toll-like receptor 2 (TLR2).	[28]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Toll-like receptor 2 (TLR2).	[29]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of Toll-like receptor 2 (TLR2).	[30]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate affects the expression of Toll-like receptor 2 (TLR2).	[31]
Beta-D-Glucose	DM5IHYP	Investigative	Beta-D-Glucose decreases the expression of Toll-like receptor 2 (TLR2).	[32]
muramyl dipeptide	DM4FR71	Investigative	muramyl dipeptide increases the activity of Toll-like receptor 2 (TLR2).	[33]
hydroxycitronellal	DMFHCV9	Investigative	hydroxycitronellal increases the expression of Toll-like receptor 2 (TLR2).	[14]

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 Toll-like receptor 2 (TLR2).	[24]

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