Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP7ML3S)

• DOT Name: Toll-like receptor 4 (TLR4)
• Synonyms: hToll; CD antigen CD284
• Gene Name: TLR4
• UniProt ID: TLR4_HUMAN
• PDB ID: 2Z62; 2Z63; 2Z65; 2Z66; 3FXI; 3UL7; 3UL8; 3UL9; 3ULA; 4G8A; 5NAM; 5NAO
• Pfam ID: PF12799 ; PF13516 ; PF13855 ; PF01582
• Sequence:
  MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLD
  LSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALG
  AFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHL
  DLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSL
  NVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDI
  IDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTS
  NKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLG
  LEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAG
  NSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPY
  KCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQL
  LVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLML
  LAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAA
  NIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLR
  QQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
• Function: Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways. At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production. In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade. In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86. Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway. In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner. Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells.
• Tissue Specificity: Highly expressed in placenta, spleen and peripheral blood leukocytes . Detected in monocytes, macrophages, dendritic cells and several types of T-cells . Expressed in pancreatic cancer cells but not in normal pancreatic cells (at protein level) .
• KEGG Pathway:
  NF-kappa B sig.ling pathway (hsa04064)
  HIF-1 sig.ling pathway (hsa04066)
  Phagosome (hsa04145)
  PI3K-Akt sig.ling pathway (hsa04151)
  Necroptosis (hsa04217)
  Neutrophil extracellular trap formation (hsa04613)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  Alcoholic liver disease (hsa04936)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Proteoglycans in cancer (hsa05205)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Inflammatory bowel disease (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Caspase activation via Death Receptors in the presence of ligand (R-HSA-140534)
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)
  MyD88 (R-HSA-166058)
  MyD88-independent TLR4 cascade (R-HSA-166166)
  TRIF-mediated programmed cell death (R-HSA-2562578)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  Activation of IRF3, IRF7 mediated by TBK1, IKK (IKBKE) (R-HSA-936964)
  IKK complex recruitment mediated by RIP1 (R-HSA-937041)
  TRAF6-mediated induction of TAK1 complex within TLR4 complex (R-HSA-937072)
  Heme signaling (R-HSA-9707616)
  IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation (R-HSA-975163)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Toll-like receptor 4 (TLR4).	[1]

47 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin affects the expression of Toll-like receptor 4 (TLR4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Toll-like receptor 4 (TLR4).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Toll-like receptor 4 (TLR4).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Toll-like receptor 4 (TLR4).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Toll-like receptor 4 (TLR4).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Toll-like receptor 4 (TLR4).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Toll-like receptor 4 (TLR4).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Toll-like receptor 4 (TLR4).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Toll-like receptor 4 (TLR4).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Toll-like receptor 4 (TLR4).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Toll-like receptor 4 (TLR4).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Toll-like receptor 4 (TLR4).	[13]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Toll-like receptor 4 (TLR4).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Toll-like receptor 4 (TLR4).	[15]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Toll-like receptor 4 (TLR4).	[16]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Toll-like receptor 4 (TLR4).	[17]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Toll-like receptor 4 (TLR4).	[18]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Toll-like receptor 4 (TLR4).	[19]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Toll-like receptor 4 (TLR4).	[20]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the expression of Toll-like receptor 4 (TLR4).	[21]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the expression of Toll-like receptor 4 (TLR4).	[22]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Toll-like receptor 4 (TLR4).	[21]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Toll-like receptor 4 (TLR4).	[23]
Glutathione	DMAHMT9	Approved	Glutathione decreases the expression of Toll-like receptor 4 (TLR4).	[25]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of Toll-like receptor 4 (TLR4).	[26]
Benazepril	DMH1M9B	Approved	Benazepril decreases the expression of Toll-like receptor 4 (TLR4).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Toll-like receptor 4 (TLR4).	[28]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Toll-like receptor 4 (TLR4).	[18]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Toll-like receptor 4 (TLR4).	[29]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Toll-like receptor 4 (TLR4).	[30]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Toll-like receptor 4 (TLR4).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Toll-like receptor 4 (TLR4).	[32]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Toll-like receptor 4 (TLR4).	[33]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Toll-like receptor 4 (TLR4).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Toll-like receptor 4 (TLR4).	[35]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Toll-like receptor 4 (TLR4).	[36]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Toll-like receptor 4 (TLR4).	[37]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Toll-like receptor 4 (TLR4).	[38]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Toll-like receptor 4 (TLR4).	[39]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the activity of Toll-like receptor 4 (TLR4).	[40]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Toll-like receptor 4 (TLR4).	[41]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Toll-like receptor 4 (TLR4).	[42]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of Toll-like receptor 4 (TLR4).	[43]
Beta-D-Glucose	DM5IHYP	Investigative	Beta-D-Glucose decreases the expression of Toll-like receptor 4 (TLR4).	[44]
24(S)-hydroxycholesterol	DMGMWA6	Investigative	24(S)-hydroxycholesterol increases the expression of Toll-like receptor 4 (TLR4).	[43]
7alpha-hydroxycholesterol	DMH6LD0	Investigative	7alpha-hydroxycholesterol increases the expression of Toll-like receptor 4 (TLR4).	[43]
muramyl dipeptide	DM4FR71	Investigative	muramyl dipeptide increases the activity of Toll-like receptor 4 (TLR4).	[45]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Morphine	DMRMS0L	Approved	Morphine affects the binding of Toll-like receptor 4 (TLR4).	[24]
Methadone	DMTW6IU	Approved	Methadone affects the binding of Toll-like receptor 4 (TLR4).	[24]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea. J Eur Acad Dermatol Venereol. 2017 Nov;31(11):1907-1911. doi: 10.1111/jdv.14437. Epub 2017 Aug 29.
• [6] Genome-wide analysis of BEAS-2B cells exposed to trivalent arsenicals and dimethylthioarsinic acid. Toxicology. 2010 Jan 31;268(1-2):31-9.
• [7] Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-B signaling pathway. Immunobiology. 2011 Mar;216(3):367-73. doi: 10.1016/j.imbio.2010.07.011. Epub 2010 Aug 19.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] Expression and modulation of progesterone induced blocking factor (PIBF) and innate immune factors in human leukemia cell lines by progesterone and mifepristone. Leuk Lymphoma. 2007 Aug;48(8):1610-7. doi: 10.1080/10428190701471999.
• [13] Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):292-8.
• [14] Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in neoplastic and non-neoplastic colonic cells in a different way. Mol Nutr Food Res. 2017 Dec;61(12). doi: 10.1002/mnfr.201700260. Epub 2017 Nov 9.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells. Br J Cancer. 2007 Oct 22;97(8):1099-105. doi: 10.1038/sj.bjc.6604003. Epub 2007 Sep 25.
• [17] Chronic ethanol exposure induces neuroinflammation in H4 cells through TLR3 / NF-B pathway and anxiety-like behavior in male C57BL/6 mice. Toxicology. 2020 Dec 15;446:152625. doi: 10.1016/j.tox.2020.152625. Epub 2020 Nov 5.
• [18] Differential effects of statins on relevant functions of human monocyte-derived dendritic cells. J Leukoc Biol. 2006 Mar;79(3):529-38. doi: 10.1189/jlb.0205064. Epub 2005 Dec 30.
• [19] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [20] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [21] Differential regulation of Toll-like receptor and CD14 pathways by retinoids and corticosteroids in human sebocytes. Dermatology. 2006;213(3):266. doi: 10.1159/000095056.
• [22] Vitamin D treatment modulates organic dust-induced cellular and airway inflammatory consequences. J Biochem Mol Toxicol. 2013 Jan;27(1):77-86. doi: 10.1002/jbt.21467. Epub 2012 Dec 20.
• [23] Adenosine reduces cell surface expression of toll-like receptor 4 and inflammation in response to lipopolysaccharide and matrix products. J Cardiovasc Transl Res. 2011 Dec;4(6):790-800. doi: 10.1007/s12265-011-9279-x. Epub 2011 May 3.
• [24] Possible involvement of toll-like receptor 4/myeloid differentiation factor-2 activity of opioid inactive isomers causes spinal proinflammation and related behavioral consequences. Neuroscience. 2010 May 19;167(3):880-93. doi: 10.1016/j.neuroscience.2010.02.011. Epub 2010 Feb 21.
• [25] Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells. Clin Exp Immunol. 2012 Apr;168(1):113-24. doi: 10.1111/j.1365-2249.2011.04549.x.
• [26] Effects of Y-27632 on the osteogenic and adipogenic potential of human dental pulp stem cells in vitro. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089003. doi: 10.1177/09603271221089003.
• [27] Expression of toll-like receptor 4, tumor necrosis factor- alpha, matrix metalloproteinase-9 and effects of benazepril in patients with acute coronary syndromes. Clin Med Insights Cardiol. 2010 Oct 11;4:89-93. doi: 10.4137/CMC.S5659.
• [28] Protective effect of resveratrol against IL-1-induced inflammatory response on human osteoarthritic chondrocytes partly via the TLR4/MyD88/NF-B signaling pathway: an "in vitro study". Int J Mol Sci. 2014 Apr 22;15(4):6925-40. doi: 10.3390/ijms15046925.
• [29] Contact allergen (PPD and DNCB)-induced keratinocyte sensitization is partly mediated through a low molecular weight hyaluronan (LMWHA)/TLR4/NF-B signaling axis. Toxicol Appl Pharmacol. 2019 Aug 15;377:114632. doi: 10.1016/j.taap.2019.114632. Epub 2019 Jun 19.
• [30] Green tea catechins alone or in combination alter functional parameters of human neutrophils via suppressing the activation of TLR-4/NFB p65 signal pathway. Toxicol In Vitro. 2015 Oct;29(7):1766-78.
• [31] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [32] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [33] Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells. Toxicol Lett. 2007 Nov 1;174(1-3):98-109. doi: 10.1016/j.toxlet.2007.08.015. Epub 2007 Sep 5.
• [34] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [35] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [36] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [37] CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
• [38] Quercetin and chrysin inhibit nickel-induced invasion and migration by downregulation of TLR4/NF-B signaling in A549?cells. Chem Biol Interact. 2018 Aug 25;292:101-109. doi: 10.1016/j.cbi.2018.07.010. Epub 2018 Jul 19.
• [39] Glucose-based peritoneal dialysis fluids downregulate toll-like receptors and trigger hyporesponsiveness to pathogen-associated molecular patterns in human peritoneal mesothelial cells. Clin Vaccine Immunol. 2010 May;17(5):757-63. doi: 10.1128/CVI.00453-09. Epub 2010 Mar 3.
• [40] Alteration of Toll-like receptor 4 activation by 4-hydroxy-2-nonenal mediated by the suppression of receptor homodimerization. Chem Biol Interact. 2009 Nov 10;182(1):59-66. doi: 10.1016/j.cbi.2009.07.009. Epub 2009 Jul 21.
• [41] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.
• [42] Apigenin and apigenin-7, 4'-O-dioctanoate protect against acrolein-aggravated inflammation via inhibiting the activation of NLRP3 inflammasome and HMGB1/MYD88/NF-B signaling pathway in Human umbilical vein endothelial cells (HUVEC). Food Chem Toxicol. 2022 Oct;168:113400. doi: 10.1016/j.fct.2022.113400. Epub 2022 Aug 31.
• [43] Loading into nanoparticles improves quercetin's efficacy in preventing neuroinflammation induced by oxysterols. PLoS One. 2014 May 6;9(5):e96795.
• [44] Fungal cell wall agents suppress the innate inflammatory cytokine responses of human peripheral blood mononuclear cells challenged with lipopolysaccharide in vitro. Int Immunopharmacol. 2011 Aug;11(8):939-47. doi: 10.1016/j.intimp.2011.02.006. Epub 2011 Feb 15.
• [45] Dendritic cell maturation induced by muramyl dipeptide (MDP) derivatives: monoacylated MDP confers TLR2/TLR4 activation. J Immunol. 2005 Jun 1;174(11):7096-103. doi: 10.4049/jimmunol.174.11.7096.