Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTD24Y0)

• DTT Name: Toll-like receptor 3 (TLR3)
• Synonyms: CD283
• Gene Name: TLR3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Toll-like receptor
• UniProt ID: TLR3_HUMAN
• TTD ID: T67894
• Sequence:
  MRQTLPCIYFWGGLLPFGMLCASSTTKCTVSHEVADCSHLKLTQVPDDLPTNITVLNLTH
  NQLRRLPAANFTRYSQLTSLDVGFNTISKLEPELCQKLPMLKVLNLQHNELSQLSDKTFA
  FCTNLTELHLMSNSIQKIKNNPFVKQKNLITLDLSHNGLSSTKLGTQVQLENLQELLLSN
  NKIQALKSEELDIFANSSLKKLELSSNQIKEFSPGCFHAIGRLFGLFLNNVQLGPSLTEK
  LCLELANTSIRNLSLSNSQLSTTSNTTFLGLKWTNLTMLDLSYNNLNVVGNDSFAWLPQL
  EYFFLEYNNIQHLFSHSLHGLFNVRYLNLKRSFTKQSISLASLPKIDDFSFQWLKCLEHL
  NMEDNDIPGIKSNMFTGLINLKYLSLSNSFTSLRTLTNETFVSLAHSPLHILNLTKNKIS
  KIESDAFSWLGHLEVLDLGLNEIGQELTGQEWRGLENIFEIYLSYNKYLQLTRNSFALVP
  SLQRLMLRRVALKNVDSSPSPFQPLRNLTILDLSNNNIANINDDMLEGLEKLEILDLQHN
  NLARLWKHANPGGPIYFLKGLSHLHILNLESNGFDEIPVEVFKDLFELKIIDLGLNNLNT
  LPASVFNNQVSLKSLNLQKNLITSVEKKVFGPAFRNLTELDMRFNPFDCTCESIAWFVNW
  INETHTNIPELSSHYLCNTPPHYHGFPVRLFDTSSCKDSAPFELFFMINTSILLIFIFIV
  LLIHFEGWRISFYWNVSVHRVLGFKEIDRQTEQFEYAAYIIHAYKDKDWVWEHFSSMEKE
  DQSLKFCLEERDFEAGVFELEAIVNSIKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAI
  EQNLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKLQVALGSK
  NSVH
• 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.
• KEGG Pathway:
  Toll-like receptor signaling pathway (hsa04620)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Influenza A (hsa05164)
  Herpes simplex infection (hsa05168)
• Reactome Pathway:
  MyD88-independent TLR3/TLR4 cascade (R-HSA-166166)
  Trafficking and processing of endosomal TLR (R-HSA-1679131)
  RIP-mediated NFkB activation via ZBP1 (R-HSA-1810476)
  TRIF-mediated programmed cell death (R-HSA-2562578)
  Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon (R-HSA-936964)
  IKK complex recruitment mediated by RIP1 (R-HSA-937041)
  TRAF6 mediated induction of TAK1 complex (R-HSA-937072)
  Ligand-dependent caspase activation (R-HSA-140534)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rintatolimod	DMYX7VI	Human immunodeficiency virus infection	1C62	Phase 3	[2]
Poly-ICLC	DM2570B	Glioblastoma multiforme	2A00.0	Phase 2	[1]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BCG65-E7	DMAMFXC	Anal intraepithelial neoplasia	2E92.5	Discontinued in Phase 3	[3]
IPH-3102	DMY3BMC	Solid tumour/cancer	2A00-2F9Z	Terminated	[4]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anti-TLR3 mabs	DMN76A4	Autoimmune diabetes	5A10	Investigative	[5]
Poly IC-poly arginine	DMXA4HY	Keratosis	ED56	Investigative	[5]
Poly-ICR	DMUMJ7B	Keratosis	ED56	Investigative	[5]
polyIC	DMV486E	Discovery agent	N.A.	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Glioma	2C82	Brainstem tissue	4.85E-01	0.63	0.83
Glioma	2C82	White matter	8.00E-01	0.11	0.1

References

• [1] Toll 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.
• [2] A 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.
• [3] Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia. Gynecol Oncol. 2010 Feb;116(2):208-12.
• [4] Trial Watch: Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology. 2012 August 1; 1(5): 699-716.
• [5] URL: 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).
• [6] Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001 Oct 18;413(6857):732-8.