Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQXAH4L)

• DOT Name: Lipopolysaccharide-binding protein (LBP)
• Synonyms: LBP
• Gene Name: LBP
• UniProt ID: LBP_HUMAN
• Pfam ID: PF01273 ; PF02886
• Sequence:
  MGALARALPSILLALLLTSTPEALGANPGLVARITDKGLQYAAQEGLLALQSELLRITLP
  DFTGDLRIPHVGRGRYEFHSLNIHSCELLHSALRPVPGQGLSLSISDSSIRVQGRWKVRK
  SFFKLQGSFDVSVKGISISVNLLLGSESSGRPTVTASSCSSDIADVEVDMSGDLGWLLNL
  FHNQIESKFQKVLESRICEMIQKSVSSDLQPYLQTLPVTTEIDSFADIDYSLVEAPRATA
  QMLEVMFKGEIFHRNHRSPVTLLAAVMSLPEEHNKMVYFAISDYVFNTASLVYHEEGYLN
  FSITDDMIPPDSNIRLTTKSFRPFVPRLARLYPNMNLELQGSVPSAPLLNFSPGNLSVDP
  YMEIDAFVLLPSSSKEPVFRLSVATNVSATLTFNTSKITGFLKPGKVKVELKESKVGLFN
  AELLEALLNYYILNTFYPKFNDKLAEGFPLPLLKRVQLYDLGLQIHKDFLFLGANVQYMR
  V
• Function: Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria. Acts as an affinity enhancer for CD14, facilitating its association with LPS. Promotes the release of cytokines in response to bacterial lipopolysaccharide.
• Tissue Specificity: Detected in blood serum (at protein level).
• KEGG Pathway:
  NF-kappa B sig.ling pathway (hsa04064)
  Toll-like receptor sig.ling pathway (hsa04620)
  Alcoholic liver disease (hsa04936)
  Tuberculosis (hsa05152)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Transfer of LPS from LBP carrier to CD14 (R-HSA-166020)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Lipopolysaccharide-binding protein (LBP) affects the response to substance of Temozolomide.	[9]
DTI-015	DMXZRW0	Approved	Lipopolysaccharide-binding protein (LBP) affects the response to substance of DTI-015.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Lipopolysaccharide-binding protein (LBP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lipopolysaccharide-binding protein (LBP).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lipopolysaccharide-binding protein (LBP).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lipopolysaccharide-binding protein (LBP).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Lipopolysaccharide-binding protein (LBP).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Lipopolysaccharide-binding protein (LBP).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Lipopolysaccharide-binding protein (LBP).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Lipopolysaccharide-binding protein (LBP).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lipopolysaccharide-binding protein (LBP).	[8]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.