Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83GJ47)

• DOT Name: Monocyte differentiation antigen CD14 (CD14)
• Synonyms: Myeloid cell-specific leucine-rich glycoprotein; CD antigen CD14
• Gene Name: CD14
• UniProt ID: CD14_HUMAN
• PDB ID: 4GLP
• Pfam ID: PF13516
• Sequence:
  MERASCLLLLLLPLVHVSATTPEPCELDDEDFRCVCNFSEPQPDWSEAFQCVSAVEVEIH
  AGGLNLEPFLKRVDADADPRQYADTVKALRVRRLTVGAAQVPAQLLVGALRVLAYSRLKE
  LTLEDLKITGTMPPLPLEATGLALSSLRLRNVSWATGRSWLAELQQWLKPGLKVLSIAQA
  HSPAFSCEQVRAFPALTSLDLSDNPGLGERGLMAALCPHKFPAIQNLALRNTGMETPTGV
  CAALAAAGVQPHSLDLSHNSLRATVNPSAPRCMWSSALNSLNLSFAGLEQVPKGLPAKLR
  VLDLSCNRLNRAPQPDELPEVDNLTLDGNPFLVPGTALPHEGSMNSGVVPACARSTLSVG
  VSGTLVLLQGARGFA
• Function: Coreceptor for bacterial lipopolysaccharide. 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(-).
• Tissue Specificity: Detected on macrophages (at protein level) . Expressed strongly on the surface of monocytes and weakly on the surface of granulocytes; also expressed by most tissue macrophages.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  NF-kappa B sig.ling pathway (hsa04064)
  Phagosome (hsa04145)
  Toll-like receptor sig.ling pathway (hsa04620)
  Hematopoietic cell lineage (hsa04640)
  Alcoholic liver disease (hsa04936)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)
  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)
  Transfer of LPS from LBP carrier to CD14 (R-HSA-166020)
  MyD88 (R-HSA-166058)
  MyD88-independent TLR4 cascade (R-HSA-166166)
  Toll Like Receptor TLR1 (R-HSA-168179)
  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)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  Neutrophil degranulation (R-HSA-6798695)
  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)
  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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Monocyte differentiation antigen CD14 (CD14).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Monocyte differentiation antigen CD14 (CD14).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Monocyte differentiation antigen CD14 (CD14).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Monocyte differentiation antigen CD14 (CD14).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Monocyte differentiation antigen CD14 (CD14).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of Monocyte differentiation antigen CD14 (CD14).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Monocyte differentiation antigen CD14 (CD14).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Monocyte differentiation antigen CD14 (CD14).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Monocyte differentiation antigen CD14 (CD14).	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Monocyte differentiation antigen CD14 (CD14).	[14]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[15]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[16]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[17]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Monocyte differentiation antigen CD14 (CD14).	[18]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[19]
Sertraline	DM0FB1J	Approved	Sertraline decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[20]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Monocyte differentiation antigen CD14 (CD14).	[21]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Monocyte differentiation antigen CD14 (CD14).	[19]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Monocyte differentiation antigen CD14 (CD14).	[22]
Ximelegatran	DMU8ANS	Approved	Ximelegatran increases the expression of Monocyte differentiation antigen CD14 (CD14).	[23]
Cimetidine	DMH61ZB	Approved	Cimetidine decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[24]
Ergotidine	DM78IME	Approved	Ergotidine affects the expression of Monocyte differentiation antigen CD14 (CD14).	[25]
Clofibrate	DMPC1J7	Approved	Clofibrate increases the expression of Monocyte differentiation antigen CD14 (CD14).	[26]
Ciprofibrate	DMGC5DB	Approved	Ciprofibrate increases the expression of Monocyte differentiation antigen CD14 (CD14).	[26]
Paricalcitol	DMYBV3G	Approved	Paricalcitol increases the expression of Monocyte differentiation antigen CD14 (CD14).	[27]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[28]
Alfacalcidol	DM1237M	Phase 4	Alfacalcidol increases the expression of Monocyte differentiation antigen CD14 (CD14).	[29]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Monocyte differentiation antigen CD14 (CD14).	[30]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Monocyte differentiation antigen CD14 (CD14).	[31]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[32]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Monocyte differentiation antigen CD14 (CD14).	[33]
Tesmilifene	DMPB36I	Discontinued in Phase 2	Tesmilifene decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Monocyte differentiation antigen CD14 (CD14).	[36]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Monocyte differentiation antigen CD14 (CD14).	[37]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Monocyte differentiation antigen CD14 (CD14).	[38]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[39]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Monocyte differentiation antigen CD14 (CD14).	[40]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the expression of Monocyte differentiation antigen CD14 (CD14).	[41]
	DM9CEI5		increases the expression of Monocyte differentiation antigen CD14 (CD14).	[42]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) increases the expression of Monocyte differentiation antigen CD14 (CD14).	[26]
Caffeic acid phenethyl ester	DMRJKIV	Investigative	Caffeic acid phenethyl ester increases the expression of Monocyte differentiation antigen CD14 (CD14).	[43]

1 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 decreases the methylation of Monocyte differentiation antigen CD14 (CD14).	[34]

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