Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCO4LP7)

• DOT Name: CD166 antigen (ALCAM)
• Synonyms: Activated leukocyte cell adhesion molecule; CD antigen CD166
• Gene Name: ALCAM
• UniProt ID: CD166_HUMAN
• PDB ID: 5A2F
• Pfam ID: PF08205 ; PF13927
• Sequence:
  MESKGASSCRLLFCLLISATVFRPGLGWYTVNSAYGDTIIIPCRLDVPQNLMFGKWKYEK
  PDGSPVFIAFRSSTKKSVQYDDVPEYKDRLNLSENYTLSISNARISDEKRFVCMLVTEDN
  VFEAPTIVKVFKQPSKPEIVSKALFLETEQLKKLGDCISEDSYPDGNITWYRNGKVLHPL
  EGAVVIIFKKEMDPVTQLYTMTSTLEYKTTKADIQMPFTCSVTYYGPSGQKTIHSEQAVF
  DIYYPTEQVTIQVLPPKNAIKEGDNITLKCLGNGNPPPEEFLFYLPGQPEGIRSSNTYTL
  TDVRRNATGDYKCSLIDKKSMIASTAITVHYLDLSLNPSGEVTRQIGDALPVSCTISASR
  NATVVWMKDNIRLRSSPSFSSLHYQDAGNYVCETALQEVEGLKKRESLTLIVEGKPQIKM
  TKKTDPSGLSKTIICHVEGFPKPAIQWTITGSGSVINQTEESPYINGRYYSKIIISPEEN
  VTLTCTAENQLERTVNSLNVSAISIPEHDEADEISDENREKVNDQAKLIVGIVVGLLLAA
  LVAGVVYWLYMKKSKTASKHVNKDLGNMEENKKLEENNHKTEA
• Function: Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts. Promotes T-cell activation and proliferation via its interactions with CD6. Contributes to the formation and maturation of the immunological synapse via its interactions with CD6. Mediates homotypic interactions with cells that express ALCAM. Acts as a ligand for the LILRB4 receptor, enhancing LILRB4-mediated inhibition of T cell proliferation. Required for normal hematopoietic stem cell engraftment in the bone marrow. Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction. Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions. Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation. Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM. Mediates outgrowth and pathfinding for retinal ganglion cell axons; [Isoform 3]: Inhibits activities of membrane-bound isoforms by competing for the same interaction partners. Inhibits cell attachment via homotypic interactions. Promotes endothelial cell migration. Inhibits endothelial cell tube formation.
• Tissue Specificity: Detected on hematopoietic stem cells derived from umbilical cord blood . Detected on lymph vessel endothelial cells, skin and tonsil . Detected on peripheral blood monocytes . Detected on monocyte-derived dendritic cells (at protein level) . Detected at low levels in spleen, placenta, liver . Expressed by activated T-cells, B-cells, monocytes and thymic epithelial cells . Isoform 1 and isoform 3 are detected in vein and artery endothelial cells, astrocytes, keratinocytes and artery smooth muscle cells . Expressed by neurons in the brain. Restricted expression in tumor cell lines. Detected in highly metastasizing melanoma cell lines .
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway: L1CAM interactions (R-HSA-373760)

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
Mitomycin	DMH0ZJE	Approved	CD166 antigen (ALCAM) affects the response to substance of Mitomycin.	[27]
NAPQI	DM8F5LR	Investigative	CD166 antigen (ALCAM) affects the response to substance of NAPQI.	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of CD166 antigen (ALCAM).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CD166 antigen (ALCAM).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CD166 antigen (ALCAM).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CD166 antigen (ALCAM).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CD166 antigen (ALCAM).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CD166 antigen (ALCAM).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CD166 antigen (ALCAM).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of CD166 antigen (ALCAM).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of CD166 antigen (ALCAM).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of CD166 antigen (ALCAM).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of CD166 antigen (ALCAM).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of CD166 antigen (ALCAM).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of CD166 antigen (ALCAM).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of CD166 antigen (ALCAM).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of CD166 antigen (ALCAM).	[14]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of CD166 antigen (ALCAM).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of CD166 antigen (ALCAM).	[16]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of CD166 antigen (ALCAM).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of CD166 antigen (ALCAM).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CD166 antigen (ALCAM).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of CD166 antigen (ALCAM).	[20]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of CD166 antigen (ALCAM).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of CD166 antigen (ALCAM).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CD166 antigen (ALCAM).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of CD166 antigen (ALCAM).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of CD166 antigen (ALCAM).	[25]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of CD166 antigen (ALCAM).	[26]

References

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