Target Information

Target General Infomation
Target ID
T82078
Former ID
TTDR00813
Target Name
Toll-like receptor 2
Gene Name
TLR2
Synonyms
TLR2
Target Type
Clinical Trial
Disease Autoimmune diabetes [ICD10: E08-E13]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Myelodysplastic syndrome [ICD9: 238.7; ICD10: D46]
Melanoma [ICD9: 172; ICD10: C43]
Prostate cancer [ICD9: 185; ICD10: C61]
Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25]
Radiation sickness [ICD9: 990; ICD10: T66]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
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 promote apoptosis in response to lipoproteins. Recognizes mycoplasmalmacrophage-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.
BioChemical Class
Toll-like receptor family
UniProt ID
O60603
Sequence
MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLS
NNRITYISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWF
KPLSSLTFLNLLGNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELE
IDASDLQSYEPKSLKSIQNVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFS
ELSTGETNSLIKKFTFRNVKITDESLFQVMKLLNQISGLLELEFDDCTLNGVGNFRASDN
DRVIDPGKVETLTIRRLHIPRFYLFYDLSTLYSLTERVKRITVENSKVFLVPCLLSQHLK
SLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQNHLASLEKTGETLLTLKNLTNIDI
SKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDVSNNNLNLFSLNLPQLK
ELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAGGNNFICSCE
FLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGMCCALFL
LILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVENLMV
QELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFS
HFRLFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRA
AIKS
Drugs and Mode of Action
Drug(s) Cadi-05 Drug Info Phase 3 Prostate cancer [522525]
MCS-18 Drug Info Phase 2 Autoimmune diabetes [529495]
OPN-305 Drug Info Phase 2 Myelodysplastic syndrome [524216]
Lipoteichoic acid Drug Info Phase 1/2 Solid tumours [548348]
MALP-2S Drug Info Phase 1/2 Pancreatic cancer [528971]
OM-174 Drug Info Phase 1 Cancer [524222]
F-50040 Drug Info Discontinued in Phase 1 Melanoma [547414]
Modulator CBLB-612 Drug Info [543472]
F-50040 Drug Info [526271]
Lipoteichoic acid Drug Info [526545]
MALP-2S Drug Info [531307]
MCS-18 Drug Info [529495]
OM-174 Drug Info [532290]
Inhibitor S-(Dimethylarsenic)Cysteine Drug Info [551393]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Phagosome
PI3K-Akt signaling pathway
Toll-like receptor signaling pathway
Legionellosis
Leishmaniasis
Chagas disease (American trypanosomiasis)
Malaria
Toxoplasmosis
Amoebiasis
Tuberculosis
Hepatitis B
Measles
Herpes simplex infection
Proteoglycans in cancer
Inflammatory bowel disease (IBD)
Rheumatoid arthritis
NetPath Pathway IL4 Signaling Pathway
TCR Signaling Pathway
PANTHER Pathway Toll receptor signaling pathway
Pathway Interaction Database Endogenous TLR signaling
Reactome Beta defensins
Mal cascade initiated on plasma membrane
TLR2 Cascade
MyD88 deficiency (TLR2/4)
IRAK4 deficiency (TLR2/4)
WikiPathways Toll-like receptor signaling pathway
IL1 and megakaryotyces in obesity
Human Complement System
Toll-Like Receptors Cascades
Mal cascade initiated on plasma membrane
Defensins
Regulation of toll-like receptor signaling pathway
References
Ref 522525ClinicalTrials.gov (NCT00810849) A Trial of Adjunctive Prednisolone and Mycobacterium w Immunotherapy in Tuberculous Pericarditis. U.S. National Institutes of Health.
Ref 524216ClinicalTrials.gov (NCT01794663) Placebo-Controlled Study to Evaluate the Safety and Efficacy of OPN-305 in Preventing Delayed Renal Graft Function. U.S. National Institutes of Health.
Ref 524222ClinicalTrials.gov (NCT01800812) Effects of OM-174 in Adult Patients With Solid Tumors. U.S. National Institutes of Health.
Ref 528971Intratumoural injection of the toll-like receptor-2/6 agonist 'macrophage-activating lipopeptide-2' in patients with pancreatic carcinoma: a phase I/II trial. Br J Cancer. 2007 Sep 3;97(5):598-604. Epub 2007 Jul 31.
Ref 529495The novel arthritis-drug substance MCS-18 attenuates the antibody production in vivo. Acta Microbiol Immunol Hung. 2008 Mar;55(1):15-31.
Ref 547414Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016041)
Ref 548348Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024869)
Ref 526271Stability and CTL-activity of P40/ELA melanoma vaccine candidate. Biologicals. 2001 Sep-Dec;29(3-4):293-8.
Ref 526545Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. J Biol Chem. 2003 May 2;278(18):15587-94. Epub 2003 Feb 19.
Ref 529495The novel arthritis-drug substance MCS-18 attenuates the antibody production in vivo. Acta Microbiol Immunol Hung. 2008 Mar;55(1):15-31.
Ref 531307Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2. Microbes Infect. 2011 Apr;13(4):350-8.
Ref 531811Treatment with OPN-305, a humanized anti-Toll-Like receptor-2 antibody, reduces myocardial ischemia/reperfusion injury in pigs. Circ Cardiovasc Interv. 2012 Apr;5(2):279-87.
Ref 532290Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors. BMC Cancer. 2013 Apr 2;13:172.
Ref 543472(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1752).
Ref 544251Trial Watch: Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology. 2012 August 1; 1(5): 699-716.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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