Target Information

Target General Infomation
Target ID
T11451
Former ID
TTDC00107
Target Name
Toll-like receptor 9
Gene Name
TLR9
Synonyms
TLR-9; TLR9
Target Type
Clinical Trial
Disease Asthma; Allergy [ICD9: 204.0, 493, 995.3; ICD10: C91.0, J45, T78.4]
Autoimmune diabetes [ICD10: E08-E13]
Asthma [ICD10: J45]
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Bacillus anthracis infection [ICD10: A22]
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Chronic lymphocytic leukaemia [ICD10: C91]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Diffuse large B-cell lymphoma [ICD9: 200; ICD10: C83.3]
Glioblastoma multiforme [ICD9: 191; ICD10: C71]
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
HBV infection [ICD9: 070.2-070.3; ICD10: B16, B18.0, B18.1]
Infections [ICD9: 001-139; ICD10: A00-B99]
Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Influenza virus [ICD10: J11.1]
Lung cancer [ICD9: 162; ICD10: C33-C34]
Leukemia [ICD9: 208.9; ICD10: C90-C95]
Prostate cancer [ICD9: 185; ICD10: C61]
Renal cell carcinoma; Solid tumours [ICD9: 140-199, 189, 210-229; ICD10: C00-C75, C64, C7A, C7B, D10-D36, D3A]
Systemic lupus erythematosus [ICD9: 710; ICD10: M32]
Function
Participates in the innate immune response to microbial agents. Detects the unmethylated cytidine-phosphate-guanosine (cpg) motivs present in bacterial dna. Acts via myd88 and traf6, leading to nf-kappa-b activation, cytokine secretion andthe inflammatory process.
BioChemical Class
Toll-like receptor family
Target Validation
T11451
UniProt ID
Q9NR96
Sequence
MGFCRSALHPLSLLVQAIMLAMTLALGTLPAFLPCELQPHGLVNCNWLFLKSVPHFSMAA
PRGNVTSLSLSSNRIHHLHDSDFAHLPSLRHLNLKWNCPPVGLSPMHFPCHMTIEPSTFL
AVPTLEELNLSYNNIMTVPALPKSLISLSLSHTNILMLDSASLAGLHALRFLFMDGNCYY
KNPCRQALEVAPGALLGLGNLTHLSLKYNNLTVVPRNLPSSLEYLLLSYNRIVKLAPEDL
ANLTALRVLDVGGNCRRCDHAPNPCMECPRHFPQLHPDTFSHLSRLEGLVLKDSSLSWLN
ASWFRGLGNLRVLDLSENFLYKCITKTKAFQGLTQLRKLNLSFNYQKRVSFAHLSLAPSF
GSLVALKELDMHGIFFRSLDETTLRPLARLPMLQTLRLQMNFINQAQLGIFRAFPGLRYV
DLSDNRISGASELTATMGEADGGEKVWLQPGDLAPAPVDTPSSEDFRPNCSTLNFTLDLS
RNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGSQFLPLTGLQVLDLSHNKLDLYHEHS
FTELPRLEALDLSYNSQPFGMQGVGHNFSFVAHLRTLRHLSLAHNNIHSQVSQQLCSTSL
RALDFSGNALGHMWAEGDLYLHFFQGLSGLIWLDLSQNRLHTLLPQTLRNLPKSLQVLRL
RDNYLAFFKWWSLHFLPKLEVLDLAGNQLKALTNGSLPAGTRLRRLDVSCNSISFVAPGF
FSKAKELRELNLSANALKTVDHSWFGPLASALQILDVSANPLHCACGAAFMDFLLEVQAA
VPGLPSRVKCGSPGQLQGLSIFAQDLRLCLDEALSWDCFALSLLAVALGLGVPMLHHLCG
WDLWYCFHLCLAWLPWRGRQSGRDEDALPYDAFVVFDKTQSAVADWVYNELRGQLEECRG
RWALRLCLEERDWLPGKTLFENLWASVYGSRKTLFVLAHTDRVSGLLRASFLLAQQRLLE
DRKDVVVLVILSPDGRRSRYVRLRQRLCRQSVLLWPHQPSGQRSFWAQLGMALTRDNHHF
YNRNFCQGPTAE
Drugs and Mode of Action
Drug(s) Cadi-05 Drug Info Phase 3 Prostate cancer [522525]
MGN-1703 Drug Info Phase 3 Colorectal cancer [524663]
SD-101 Drug Info Phase 3 HCV infection [525113]
BL-7040 Drug Info Phase 2 Inflammatory bowel disease [523753]
CpG-10101 Drug Info Phase 2 HCV infection [521786]
CYT003 Drug Info Phase 2 Asthma [533260]
IMO-2055 Drug Info Phase 2 Renal cell carcinoma; Solid tumours [550998]
JVRS-100 Drug Info Phase 2 Leukemia [522718]
MIS-416 Drug Info Phase 2 Autoimmune diabetes [549949]
Tolamba Drug Info Phase 2 Allergic rhinitis [522129]
Zadaxin/lamivudine Drug Info Phase 2 HBV infection [549869]
AZD1419 Drug Info Phase 1 Asthma [548372]
CPG 52364 Drug Info Phase 1 Systemic lupus erythematosus [532501]
GNKG-168 Drug Info Phase 1 Chronic lymphocytic leukaemia [524153]
IMO-2125 Drug Info Phase 1 HCV infection [550998]
IMO-3100 Drug Info Phase 1 Autoimmune diabetes [550998]
Litenimod Drug Info Phase 1 Glioblastoma multiforme [551464]
MGN-1706 Drug Info Phase 1 Cancer [525374]
N-8295 Drug Info Phase 1 Influenza virus [549878]
SAR-21609 Drug Info Phase 1 Asthma [530837]
IMO-2134 Drug Info Preclinical Asthma; Allergy [550998]
IR-103 Drug Info Discontinued in Phase 3 Human immunodeficiency virus infection [547777]
Agatolimod Drug Info Discontinued in Phase 2 Lung cancer [547005]
IM0-8400 Drug Info Discontinued in Phase 1/2 Diffuse large B-cell lymphoma [550999]
DV-1179 Drug Info Discontinued in Phase 1 Systemic lupus erythematosus [549321]
AVE0675 Drug Info Terminated Asthma [548655]
Agonist Agatolimod Drug Info [536475], [549974]
AVE0675 Drug Info [549823]
AZD1419 Drug Info [549879]
CpG-10101 Drug Info [528995]
CYT003 Drug Info [533260]
IMO-2055 Drug Info [550998]
IMO-2125 Drug Info [550998]
IMO-2134 Drug Info [550998]
MGN-1703 Drug Info [532775]
MGN-1706 Drug Info [543477]
SAR-21609 Drug Info [544251]
Activator BL-7040 Drug Info [533251]
Antagonist CPG 52364 Drug Info [551089]
IM0-8400 Drug Info [551000]
Modulator DIMS-9054 Drug Info [543477]
DV-1179 Drug Info
GNKG-168 Drug Info [550450]
IMO-3100 Drug Info
Litenimod Drug Info [543477]
MIS-416 Drug Info
Zadaxin/lamivudine Drug Info [527615]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Toll-like receptor signaling pathway
Chagas disease (American trypanosomiasis)
African trypanosomiasis
Malaria
Tuberculosis
Measles
Herpes simplex infection
NetPath Pathway BCR Signaling Pathway
PANTHER Pathway Toll receptor signaling pathway
Reactome PI3K Cascade
Trafficking and processing of endosomal TLR
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
MyD88 dependent cascade initiated on endosome
WikiPathways Toll-like receptor signaling pathway
Toll-Like Receptors Cascades
MyD88 dependent cascade initiated on endosome
Trafficking and processing of endosomal TLR
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
Regulation of toll-like receptor signaling pathway
References
Ref 521786ClinicalTrials.gov (NCT00277238) CPG10101 Combination Therapy For The Treatment Of Hepatitis C In Non-Responder (Null And Partial Responder) Hepatitis C Virus (HCV) Genotype 1 Infected Subjects. U.S.National Institutes of Health.
Ref 522129ClinicalTrials.gov (NCT00537355) An Evaluation of the Efficacy and Safety of TOLAMBA for Ragweed-Allergic Rhinitis in an Environmental Exposure Chamber. U.S. National Institutes of Health.
Ref 522525ClinicalTrials.gov (NCT00810849) A Trial of Adjunctive Prednisolone and Mycobacterium w Immunotherapy in Tuberculous Pericarditis. U.S. National Institutes of Health.
Ref 522718ClinicalTrials.gov (NCT00936468) Safety, Tolerability and Immunogenicity of Fluzone With and Without JVRS-100 in Elderly Subjects. U.S. National Institutes of Health.
Ref 523753ClinicalTrials.gov (NCT01506362) Efficacy, Pharmacodynamics, Safety and Tolerability of Oral BL-7040 in Patients With Moderately Active Ulcerative Colitis. U.S. National Institutes of Health.
Ref 524153ClinicalTrials.gov (NCT01743807) Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia. U.S. National Institutes of Health.
Ref 524663ClinicalTrials.gov (NCT02077868) Evaluation of MGN1703 Maintenance Treatment in Patients With mCRC With Tumor Reduction During Induction Treatment. U.S. National Institutes of Health.
Ref 525113ClinicalTrials.gov (NCT02384460) Study of Efficacy and Safety of SD-101 Cream in Patients With Epidermolysis Bullosa. U.S. National Institutes of Health.
Ref 525374Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov. 2010 Apr;9(4):293-307. doi: 10.1038/nrd3203.
Ref 530837Targeting Toll-like receptors: emerging therapeutics. Nat Rev Drug Discov. 2010 Apr;9(4):293-307.
Ref 532501Treatment of systemic lupus erythematosus: new therapeutic avenues and blind alleys. Nat Rev Rheumatol. 2014 Jan;10(1):23-34.
Ref 533260CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study. Allergy. 2015 Sep;70(9):1160-8.
Ref 547005Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011959)
Ref 547777Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019204)
Ref 548372Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025034)
Ref 548655Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027402)
Ref 549321Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035150)
Ref 549869Clinical pipeline report, company report or official report of SciClone.
Ref 549878Clinical pipeline report, company report or official report of Dynavax Technologies Corp.
Ref 549949Targeting Innate Receptors with MIS416 Reshapes Th Responses and Suppresses CNS Disease in a Mouse Model of Multiple Sclerosis. PLoS ONE 9(1): e87712. January 31, 2014.
Ref 550998Clinical pipeline report, company report or official report of Idera Pharmaceuticals (2011).
Ref 550999Clinical pipeline report, company report or official report of Idera Pharmaceuticals.
Ref 551464Clinical pipeline report, company report or official report of Oligovax SAS.
Ref 527615Zadaxin (thymosin alpha1) for the treatment of viral hepatitis. Expert Opin Investig Drugs. 1999 Mar;8(3):281-7.
Ref 528995Safety, pharmacokinetics and immune effects in normal volunteers of CPG 10101 (ACTILON), an investigational synthetic toll-like receptor 9 agonist. Antivir Ther. 2007;12(5):741-51.
Ref 532775Maintenance treatment with the immunomodulator MGN1703, a Toll-like receptor 9 (TLR9) agonist, in patients with metastatic colorectal carcinoma and disease control after chemotherapy: a randomised, double-blind, placebo-controlled trial. J Cancer Res Clin Oncol. 2014 Sep;140(9):1615-24.
Ref 533251Gut feeling: MicroRNA discriminators of the intestinal TLR9-cholinergic links. Int Immunopharmacol. 2015 May 20. pii: S1567-5769(15)00231-3.
Ref 533260CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study. Allergy. 2015 Sep;70(9):1160-8.
Ref 536475CPG-7909 (PF-3512676, ProMune): toll-like receptor-9 agonist in cancer therapy. Expert Opin Biol Ther. 2007 Aug;7(8):1257-66.
Ref 543477(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: 1759).
Ref 544078Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone?) increases antibody response, cellular immunity, and antigenically drifted protection. Vaccine. 2009 June 12; 27(29):3811-3820.
Ref 544095Phase II study of a TLR-9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma. Br J Haematol. 2009 August; 146(3): 282-291.
Ref 544251Trial Watch: Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology. 2012 August 1; 1(5): 699-716.
Ref 544459Novel drugs targeting Toll-like receptors for antiviral therapy. Future Virol. 2014 September; 9(9): 811-829.
Ref 547845Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019871)
Ref 549823Pharma & Vaccines. Product Development Pipeline. April 29 2009.
Ref 549879Clinical pipeline report, company report or official report of dynavax.
Ref 549949Targeting Innate Receptors with MIS416 Reshapes Th Responses and Suppresses CNS Disease in a Mouse Model of Multiple Sclerosis. PLoS ONE 9(1): e87712. January 31, 2014.
Ref 549974Pfizer. Product Development Pipeline. March 31 2009.
Ref 550450National Cancer Institute Drug Dictionary (drug id 662816).
Ref 550998Clinical pipeline report, company report or official report of Idera Pharmaceuticals (2011).
Ref 551000Clinical pipeline report, company report or official report of Idera Pharmaceuticals.
Ref 551089Coley Pharmaceutical Group Diversifies Pipeline with First-in-Class TLR Antagonist for the Treatment of Systemic Lupus Erythematosus. Lupus Foundation of America, Inc. 2007.

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