Target Information

Target General Infomation
Target ID
T67894
Former ID
TTDC00007
Target Name
Toll-like receptor 3
Gene Name
TLR3
Synonyms
CD283; TLR3
Target Type
Clinical Trial
Disease Anal intraepithelial neoplasia; Human papillomavirus infections [ICD9:154, 078.1079.4; ICD10: C21, B97.7]
Autoimmune diabetes [ICD10: E08-E13]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Glioblastoma multiforme [ICD9: 191; ICD10: C71]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Keratosis [ICD10: L57.0]
Function
Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response.
BioChemical Class
Toll-like receptor family
Target Validation
T67894
UniProt ID
O15455
Sequence
MRQTLPCIYFWGGLLPFGMLCASSTTKCTVSHEVADCSHLKLTQVPDDLPTNITVLNLTH
NQLRRLPAANFTRYSQLTSLDVGFNTISKLEPELCQKLPMLKVLNLQHNELSQLSDKTFA
FCTNLTELHLMSNSIQKIKNNPFVKQKNLITLDLSHNGLSSTKLGTQVQLENLQELLLSN
NKIQALKSEELDIFANSSLKKLELSSNQIKEFSPGCFHAIGRLFGLFLNNVQLGPSLTEK
LCLELANTSIRNLSLSNSQLSTTSNTTFLGLKWTNLTMLDLSYNNLNVVGNDSFAWLPQL
EYFFLEYNNIQHLFSHSLHGLFNVRYLNLKRSFTKQSISLASLPKIDDFSFQWLKCLEHL
NMEDNDIPGIKSNMFTGLINLKYLSLSNSFTSLRTLTNETFVSLAHSPLHILNLTKNKIS
KIESDAFSWLGHLEVLDLGLNEIGQELTGQEWRGLENIFEIYLSYNKYLQLTRNSFALVP
SLQRLMLRRVALKNVDSSPSPFQPLRNLTILDLSNNNIANINDDMLEGLEKLEILDLQHN
NLARLWKHANPGGPIYFLKGLSHLHILNLESNGFDEIPVEVFKDLFELKIIDLGLNNLNT
LPASVFNNQVSLKSLNLQKNLITSVEKKVFGPAFRNLTELDMRFNPFDCTCESIAWFVNW
INETHTNIPELSSHYLCNTPPHYHGFPVRLFDTSSCKDSAPFELFFMINTSILLIFIFIV
LLIHFEGWRISFYWNVSVHRVLGFKEIDRQTEQFEYAAYIIHAYKDKDWVWEHFSSMEKE
DQSLKFCLEERDFEAGVFELEAIVNSIKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAI
EQNLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKLQVALGSK
NSVH
Drugs and Mode of Action
Drug(s) Rintatolimod Drug Info Phase 3 Human immunodeficiency virus infection [524780]
Poly-ICLC Drug Info Phase 2 Glioblastoma multiforme [528669]
BCG65-E7 Drug Info Discontinued in Phase 3 Anal intraepithelial neoplasia; Human papillomavirus infections [546672]
IPH-3102 Drug Info Terminated Cancer [549463]
Modulator Anti-TLR3 mabs Drug Info [543473]
Agonist BCG65-E7 Drug Info [537086], [537528]
IPH-3102 Drug Info [544251]
Poly-ICR Drug Info [543473]
polyIC Drug Info [526173]
Inducer Poly-ICLC Drug Info [528669]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Toll-like receptor signaling pathway
Hepatitis C
Hepatitis B
Influenza A
Herpes simplex infection
NetPath Pathway TCR Signaling Pathway
PANTHER Pathway Toll receptor signaling pathway
Pathway Interaction Database Endogenous TLR signaling
Reactome Ligand-dependent caspase activation
MyD88-independent TLR3/TLR4 cascade
Trafficking and processing of endosomal TLR
RIP-mediated NFkB activation via ZBP1
TRIF-mediated programmed cell death
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
IKK complex recruitment mediated by RIP1
TRAF6 mediated induction of TAK1 complex
WikiPathways Toll-like receptor signaling pathway
Cytosolic sensors of pathogen-associated DNA
Toll-Like Receptors Cascades
MyD88-independent cascade
Trafficking and processing of endosomal TLR
Regulation of toll-like receptor signaling pathway
References
Ref 524780ClinicalTrials.gov (NCT02151448) alphaDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as Adjuvant Treatment of Peritoneal Surface Malignancies. U.S. National Institutes of Health.
Ref 528669Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. J Transl Med. 2007 Feb 12;5:10.
Ref 546672Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009576)
Ref 549463Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037691)
Ref 526173Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001 Oct 18;413(6857):732-8.
Ref 528669Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. J Transl Med. 2007 Feb 12;5:10.
Ref 531850A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome. PLoS One. 2012;7(3):e31334.
Ref 537086Medical treatment of cervical intraepithelial neoplasia II, III: an update review. Int J Clin Oncol. 2009 Feb;14(1):37-42. Epub 2009 Feb 20.
Ref 537528Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia. Gynecol Oncol. 2009 Jun 23.
Ref 543473(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: 1753).
Ref 544251Trial Watch: Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology. 2012 August 1; 1(5): 699-716.

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