Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6I7DC)

• DTT Name: Monocyte differentiation antigen CD14 (CD14)
• Synonyms: Myeloid cell-specific leucine-rich glycoprotein
• Gene Name: CD14
• DTT Type: Clinical trial target; [1]
• UniProt ID: CD14_HUMAN
• TTD ID: T23212
• Sequence:
  MERASCLLLLLLPLVHVSATTPEPCELDDEDFRCVCNFSEPQPDWSEAFQCVSAVEVEIH
  AGGLNLEPFLKRVDADADPRQYADTVKALRVRRLTVGAAQVPAQLLVGALRVLAYSRLKE
  LTLEDLKITGTMPPLPLEATGLALSSLRLRNVSWATGRSWLAELQQWLKPGLKVLSIAQA
  HSPAFSCEQVRAFPALTSLDLSDNPGLGERGLMAALCPHKFPAIQNLALRNTGMETPTGV
  CAALAAAGVQPHSLDLSHNSLRATVNPSAPRCMWSSALNSLNLSFAGLEQVPKGLPAKLR
  VLDLSCNRLNRAPQPDELPEVDNLTLDGNPFLVPGTALPHEGSMNSGVVPACARSTLSVG
  VSGTLVLLQGARGFA
• Function: In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Acts as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-). Coreceptor for bacterial lipopolysaccharide.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  NF-kappa B signaling pathway (hsa04064)
  Phagosome (hsa04145)
  Toll-like receptor signaling pathway (hsa04620)
  Hematopoietic cell lineage (hsa04640)
  Regulation of actin cytoskeleton (hsa04810)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Transcriptional misregulation in cancer (hsa05202)
• Reactome Pathway:
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)
  MyD88 (R-HSA-166058)
  MyD88-independent TLR3/TLR4 cascade (R-HSA-166166)
  Toll Like Receptor TLR6 (R-HSA-168188)
  TRIF-mediated programmed cell death (R-HSA-2562578)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon (R-HSA-936964)
  IKK complex recruitment mediated by RIP1 (R-HSA-937041)
  TRAF6 mediated induction of TAK1 complex (R-HSA-937072)
  Ligand-dependent caspase activation (R-HSA-140534)

Molecular Interaction Atlas (MIA) of This DTT

1 Drugs in Phase 2 Trial Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IC14	DM37CX4	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2 Trial	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Neonatal sepsis	1G41	Whole blood	5.74E-14	1.61	1.11

References

• [1] IC14, a CD14 specific monoclonal antibody, is a potential treatment for patients with severe sepsis. J Endotoxin Res. 2001;7(4):310-4.