Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8CWFK)

• DTT Name: Toll-like receptor 8 (TLR8)
• Synonyms: UNQ249/PRO286; CD288 antigen; CD288
• Gene Name: TLR8
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Toll-like receptor
• UniProt ID: TLR8_HUMAN
• TTD ID: T48703
• Sequence:
  MENMFLQSSMLTCIFLLISGSCELCAEENFSRSYPCDEKKQNDSVIAECSNRRLQEVPQT
  VGKYVTELDLSDNFITHITNESFQGLQNLTKINLNHNPNVQHQNGNPGIQSNGLNITDGA
  FLNLKNLRELLLEDNQLPQIPSGLPESLTELSLIQNNIYNITKEGISRLINLKNLYLAWN
  CYFNKVCEKTNIEDGVFETLTNLELLSLSFNSLSHVPPKLPSSLRKLFLSNTQIKYISEE
  DFKGLINLTLLDLSGNCPRCFNAPFPCVPCDGGASINIDRFAFQNLTQLRYLNLSSTSLR
  KINAAWFKNMPHLKVLDLEFNYLVGEIASGAFLTMLPRLEILDLSFNYIKGSYPQHINIS
  RNFSKLLSLRALHLRGYVFQELREDDFQPLMQLPNLSTINLGINFIKQIDFKLFQNFSNL
  EIIYLSENRISPLVKDTRQSYANSSSFQRHIRKRRSTDFEFDPHSNFYHFTRPLIKPQCA
  AYGKALDLSLNSIFFIGPNQFENLPDIACLNLSANSNAQVLSGTEFSAIPHVKYLDLTNN
  RLDFDNASALTELSDLEVLDLSYNSHYFRIAGVTHHLEFIQNFTNLKVLNLSHNNIYTLT
  DKYNLESKSLVELVFSGNRLDILWNDDDNRYISIFKGLKNLTRLDLSLNRLKHIPNEAFL
  NLPASLTELHINDNMLKFFNWTLLQQFPRLELLDLRGNKLLFLTDSLSDFTSSLRTLLLS
  HNRISHLPSGFLSEVSSLKHLDLSSNLLKTINKSALETKTTTKLSMLELHGNPFECTCDI
  GDFRRWMDEHLNVKIPRLVDVICASPGDQRGKSIVSLELTTCVSDVTAVILFFFTFFITT
  MVMLAALAHHLFYWDVWFIYNVCLAKVKGYRSLSTSQTFYDAYISYDTKDASVTDWVINE
  LRYHLEESRDKNVLLCLEERDWDPGLAIIDNLMQSINQSKKTVFVLTKKYAKSWNFKTAF
  YLALQRLMDENMDVIIFILLEPVLQHSQYLRLRQRICKSSILQWPDNPKAEGLFWQTLRN
  VVLTENDSRYNNMYVDSIKQY
• 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. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.
• KEGG Pathway: Toll-like receptor signaling pathway (hsa04620)
• Reactome Pathway:
  TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling (R-HSA-975110)
  TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (R-HSA-975138)
  MyD88 dependent cascade initiated on endosome (R-HSA-975155)
  Trafficking and processing of endosomal TLR (R-HSA-1679131)

Molecular Interaction Atlas (MIA) of This DTT

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Afimetoran	DM3HN3U	Systemic lupus erythematosus	4A40.0	Phase 2	[2]
Resiquimod	DML6XSP	Actinic keratosis	EK90.0	Phase 2	[3]
Selgantolimod	DMST4OR	Hepatitis B	1E51	Phase 2	[4]
NKTR-262	DMYR8LF	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[5]
CPG 52364	DMVDYTG	Systemic lupus erythematosus	4A40.0	Phase 1	[6]
CV8102	DMYD37G	Melanoma	2C30	Phase 1	[7]
DN1508052	DM0JT9C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
GSK5251738	DM8Y6DR	Hepatitis B	1E51	Phase 1	[9]
MEDI9197	DM0J7UR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
SBT6050	DMHBD3T	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
VTX-1463	DM4ZIRK	Allergic rhinitis	CA08.0	Phase 1	[12]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VTX-2337	DMLCTBP	Allergy	4A80-4A85	Discontinued in Phase 2	[1]
IM0-8400	DMEF9JW	Diffuse large B-cell lymphoma	2A81	Discontinued in Phase 1/2	[13]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ODN-1411	DM0GVZO	Rheumatoid arthritis	FA20	Investigative	[14]
VTX-744	DMEVAIF	Discovery agent	N.A.	Investigative	[15]
VTX-763	DMGTB95	Autoimmune diabetes	5A10	Investigative	[15]

References

• [1] Clinical pipeline report, company report or official report of Array BioPharma (Drug: Motolimod / VTX2337).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [3] TLR agonists as vaccine adjuvants: comparison of CpG ODN and Resiquimod (R-848).Vaccine.2005 Nov 1;23(45):5263-70.
• [4] Discovery of GS-9688 (Selgantolimod) as a Potent and Selective Oral Toll-Like Receptor 8 Agonist for the Treatment of Chronic Hepatitis B. J Med Chem. 2020 Sep 24;63(18):10188-10203.
• [5] Clinical pipeline report, company report or official report of Nektar Therapeutics.
• [6] Coley Pharmaceutical Group Diversifies Pipeline with First-in-Class TLR Antagonist for the Treatment of Systemic Lupus Erythematosus. Lupus Foundation of America, Inc. 2007.
• [7] Clinical pipeline report, company report or official report of CureVac.
• [8] Clinical pipeline report, company report or official report of Shanghai De Novo Pharmatech.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Clinical pipeline report, company report or official report of Silverback Therapeutics.
• [12] VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis. Expert Opin Investig Drugs. 2011 Jul;20(7):981-6.
• [13] Clinical pipeline report, company report or official report of Idera Pharmaceuticals.
• [14] Oligodeoxynucleotide inhibition of Toll-like receptors 3, 7, 8, and 9 suppresses cytokine production in a human rheumatoid arthritis model. Eur J Immunol. 2016 Mar;46(3):772-81.
• [15] 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: 1758).