Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T81443
|
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| Former ID |
TTDC00209
|
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| Target Name |
Toll-like receptor 4
|
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| Gene Name |
TLR4
|
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| Synonyms |
HToll; TLR-4; TLR4
|
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| Target Type |
Clinical Trial
|
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| Disease | Autoimmune diabetes [ICD10: E08-E13] | ||||
| Allergy [ICD9: 995.3; ICD10: T78.4] | |||||
| Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
| Hepatitis virus infection [ICD9: 573.3; ICD10: K75.9] | |||||
| Melanoma [ICD9: 172; ICD10: C43] | |||||
| Prostate cancer [ICD9: 185; ICD10: C61] | |||||
| Sepsis [ICD9: 995.91; ICD10: A40, A41] | |||||
| Septic shock [ICD9: 785.52; ICD10: A41.9] | |||||
| Function |
Cooperates with ly96 and cd14 to mediate the innate immune response to bacterial lipopolysaccharide (lps). Acts via myd88, tirap and traf6, leading to nf-kappa-b activation, cytokine secretion and the inflammatoryresponse.
|
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| BioChemical Class |
Toll-like receptor family
|
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| Target Validation |
T81443
|
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| UniProt ID | |||||
| Sequence |
MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLD
LSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALG AFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHL DLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSL NVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDI IDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTS NKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLG LEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAG NSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPY KCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQL LVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLML LAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAA NIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLR QQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI |
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| Drugs and Mode of Action | |||||
| Drug(s) | MPL-containing Pollinex allergy desensitization vaccine | Drug Info | Preregistration | Allergy | [1] |
| Cadi-05 | Drug Info | Phase 3 | Prostate cancer | [2] | |
| ERITORAN | Drug Info | Phase 3 | Septic shock | [3], [4] | |
| Resatorvid | Drug Info | Phase 3 | Sepsis | [5] | |
| CRX-675 | Drug Info | Phase 1 | Hepatitis virus infection | [6] | |
| NI-0101 | Drug Info | Phase 1 | Autoimmune diabetes | [7] | |
| OM-174 | Drug Info | Phase 1 | Cancer | [8] | |
| CS-4771 | Drug Info | Discontinued in Phase 1 | Sepsis | [9] | |
| LZ-8 | Drug Info | Terminated | Autoimmune diabetes | [10] | |
| Inhibitor | 3-Hydroxy-Myristic Acid | Drug Info | [11] | ||
| 6-(2-aminophenoxy)benzo[d]isothiazol-3-amine | Drug Info | [12] | |||
| CRX-526 | Drug Info | [13] | |||
| ERITORAN | Drug Info | [12] | |||
| Lauric Acid | Drug Info | [11] | |||
| MYRISTIC ACID | Drug Info | [14] | |||
| Modulator | AS04 | Drug Info | [15] | ||
| CS-4771 | Drug Info | [16] | |||
| LZ-8 | Drug Info | [15] | |||
| OM-174 | Drug Info | [17] | |||
| OM-197-MP-AC | Drug Info | [15] | |||
| OM-294-DP | Drug Info | [15] | |||
| Agonist | CRX-675 | Drug Info | [15] | ||
| Antagonist | Resatorvid | Drug Info | [18], [19], [20] | ||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| Pathways | |||||
| KEGG Pathway | NF-kappa B signaling pathway | ||||
| HIF-1 signaling pathway | |||||
| Phagosome | |||||
| PI3K-Akt signaling pathway | |||||
| Toll-like receptor signaling pathway | |||||
| Pathogenic Escherichia coli infection | |||||
| Salmonella infection | |||||
| Pertussis | |||||
| Legionellosis | |||||
| Leishmaniasis | |||||
| Chagas disease (American trypanosomiasis) | |||||
| Malaria | |||||
| Toxoplasmosis | |||||
| Amoebiasis | |||||
| Tuberculosis | |||||
| Hepatitis B | |||||
| Measles | |||||
| Influenza A | |||||
| Proteoglycans in cancer | |||||
| Inflammatory bowel disease (IBD) | |||||
| Rheumatoid arthritis | |||||
| NetPath Pathway | IL5 Signaling Pathway | ||||
| IL2 Signaling Pathway | |||||
| IL4 Signaling Pathway | |||||
| PANTHER Pathway | Toll receptor signaling pathway | ||||
| Pathway Interaction Database | Endogenous TLR signaling | ||||
| Reactome | Ligand-dependent caspase activation | ||||
| Toll Like Receptor 4 (TLR4) Cascade | |||||
| Mal cascade initiated on plasma membrane | |||||
| MyD88-independent TLR3/TLR4 cascade | |||||
| TRIF-mediated programmed cell death | |||||
| MyD88 deficiency (TLR2/4) | |||||
| IRAK4 deficiency (TLR2/4) | |||||
| 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 | ||||
| Toll-Like Receptors Cascades | |||||
| Mal cascade initiated on plasma membrane | |||||
| MyD88-independent cascade | |||||
| Primary Focal Segmental Glomerulosclerosis FSGS | |||||
| Spinal Cord Injury | |||||
| Corticotropin-releasing hormone | |||||
| Pathogenic Escherichia coli infection | |||||
| Regulation of toll-like receptor signaling pathway | |||||
| References | |||||
| REF 1 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010983) | ||||
| REF 2 | ClinicalTrials.gov (NCT00810849) A Trial of Adjunctive Prednisolone and Mycobacterium w Immunotherapy in Tuberculous Pericarditis. U.S. National Institutes of Health. | ||||
| REF 3 | (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. (Ligand id: 4919). | ||||
| REF 4 | ClinicalTrials.gov (NCT00334828) ACCESS: A Controlled Comparison of Eritoran Tetrasodium and Placebo in Patients With Severe Sepsis. U.S. National Institutes of Health. | ||||
| REF 5 | ClinicalTrials.gov (NCT00633477) Efficacy and Safety of Resatorvid in Patients With Sepsis-induced Cardiovascular and Respiratory Failure. U.S. National Institutes of Health. | ||||
| REF 6 | ClinicalTrials.gov (NCT00076037) Safety of and Immune Response to a New HIV Vaccine: HIV CTL MEP. U.S. National Institutes of Health. | ||||
| REF 7 | ClinicalTrials.gov (NCT01808469) First in Human Study of an Anti-Toll-like Receptor 4 (TLR4) Monoclonal Antibody (NI-0101) in Adult Healthy Volunteers. U.S. National Institutes of Health. | ||||
| REF 8 | ClinicalTrials.gov (NCT01800812) Effects of OM-174 in Adult Patients With Solid Tumors. U.S. National Institutes of Health. | ||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032166) | ||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006001) | ||||
| REF 11 | How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
| REF 12 | J Med Chem. 2008 Nov 13;51(21):6621-6. Epub 2008 Oct 2.Small molecule modulators of toll-like receptors. | ||||
| REF 13 | Bioorg Med Chem Lett. 2008 Oct 15;18(20):5350-4. Epub 2008 Sep 19.The 'Ethereal' nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics. | ||||
| REF 14 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | ||||
| REF 15 | (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: 1754). | ||||
| REF 16 | Eritoran insight for influenza treatment. SciBX 6(19); doi:10.1038/scibx.2013.453. May 16 2013 | ||||
| REF 17 | Phase 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 18 | TAK-242 selectively suppresses Toll-like receptor 4-signaling mediated by the intracellular domain. Eur J Pharmacol. 2008 Apr 14;584(1):40-8. Epub 2008 Feb 5. | ||||
| REF 19 | Clinical pipeline report, company report or official report of Takeda (2009). | ||||
| REF 20 | THE NOVEL SELECTIVE TOLL-LIKE RECEPTOR 4 SIGNAL TRANSDUCTION INHIBITOR TAK-242 PREVENTS ENDOTOXAEMIA IN CONSCIOUS GUINEA-PIGS. Clinical and Experimental Pharmacology and Physiology Volume 36, Issue 5-6, pages 589-593, May/June 2009 | ||||
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