Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDHBU0N)

• DOT Name: Lymphocyte antigen 75 (LY75)
• Synonyms: Ly-75; C-type lectin domain family 13 member B; DEC-205; gp200-MR6; CD antigen CD205
• Gene Name: LY75
• UniProt ID: LY75_HUMAN
• PDB ID: 7JPT; 7JPU; 8HBC
• Pfam ID: PF00040 ; PF00059
• Sequence:
  MRTGWATPRRPAGLLMLLFWFFDLAEPSGRAANDPFTIVHGNTGKCIKPVYGWIVADDCD
  ETEDKLWKWVSQHRLFHLHSQKCLGLDITKSVNELRMFSCDSSAMLWWKCEHHSLYGAAR
  YRLALKDGHGTAISNASDVWKKGGSEESLCDQPYHEIYTRDGNSYGRPCEFPFLIDGTWH
  HDCILDEDHSGPWCATTLNYEYDRKWGICLKPENGCEDNWEKNEQFGSCYQFNTQTALSW
  KEAYVSCQNQGADLLSINSAAELTYLKEKEGIAKIFWIGLNQLYSARGWEWSDHKPLNFL
  NWDPDRPSAPTIGGSSCARMDAESGLWQSFSCEAQLPYVCRKPLNNTVELTDVWTYSDTR
  CDAGWLPNNGFCYLLVNESNSWDKAHAKCKAFSSDLISIHSLADVEVVVTKLHNEDIKEE
  VWIGLKNINIPTLFQWSDGTEVTLTYWDENEPNVPYNKTPNCVSYLGELGQWKVQSCEEK
  LKYVCKRKGEKLNDASSDKMCPPDEGWKRHGETCYKIYEDEVPFGTNCNLTITSRFEQEY
  LNDLMKKYDKSLRKYFWTGLRDVDSCGEYNWATVGGRRRAVTFSNWNFLEPASPGGCVAM
  STGKSVGKWEVKDCRSFKALSICKKMSGPLGPEEASPKPDDPCPEGWQSFPASLSCYKVF
  HAERIVRKRNWEEAERFCQALGAHLSSFSHVDEIKEFLHFLTDQFSGQHWLWIGLNKRSP
  DLQGSWQWSDRTPVSTIIMPNEFQQDYDIRDCAAVKVFHRPWRRGWHFYDDREFIYLRPF
  ACDTKLEWVCQIPKGRTPKTPDWYNPDRAGIHGPPLIIEGSEYWFVADLHLNYEEAVLYC
  ASNHSFLATITSFVGLKAIKNKIANISGDGQKWWIRISEWPIDDHFTYSRYPWHRFPVTF
  GEECLYMSAKTWLIDLGKPTDCSTKLPFICEKYNVSSLEKYSPDSAAKVQCSEQWIPFQN
  KCFLKIKPVSLTFSQASDTCHSYGGTLPSVLSQIEQDFITSLLPDMEATLWIGLRWTAYE
  KINKWTDNRELTYSNFHPLLVSGRLRIPENFFEEESRYHCALILNLQKSPFTGTWNFTSC
  SERHFVSLCQKYSEVKSRQTLQNASETVKYLNNLYKIIPKTLTWHSAKRECLKSNMQLVS
  ITDPYQQAFLSVQALLHNSSLWIGLFSQDDELNFGWSDGKRLHFSRWAETNGQLEDCVVL
  DTDGFWKTVDCNDNQPGAICYYSGNETEKEVKPVDSVKCPSPVLNTPWIPFQNCCYNFII
  TKNRHMATTQDEVHTKCQKLNPKSHILSIRDEKENNFVLEQLLYFNYMASWVMLGITYRN
  KSLMWFDKTPLSYTHWRAGRPTIKNEKFLAGLSTDGFWDIQTFKVIEEAVYFHQHSILAC
  KIEMVDYKEEYNTTLPQFMPYEDGIYSVIQKKVTWYEALNMCSQSGGHLASVHNQNGQLF
  LEDIVKRDGFPLWVGLSSHDGSESSFEWSDGSTFDYIPWKGQTSPGNCVLLDPKGTWKHE
  KCNSVKDGAICYKPTKSKKLSRLTYSSRCPAAKENGSRWIQYKGHCYKSDQALHSFSEAK
  KLCSKHDHSATIVSIKDEDENKFVSRLMRENNNITMRVWLGLSQHSVDQSWSWLDGSEVT
  FVKWENKSKSGVGRCSMLIASNETWKKVECEHGFGRVVCKVPLGPDYTAIAIIVATLSIL
  VLMGGLIWFLFQRHRLHLAGFSSVRYAQGVNEDEIMLPSFHD
• Function: Acts as an endocytic receptor to direct captured antigens from the extracellular space to a specialized antigen-processing compartment. Causes reduced proliferation of B-lymphocytes.
• Tissue Specificity: Expressed in spleen, thymus, colon and peripheral blood lymphocytes. Detected in myeloid and B-lymphoid cell lines. Isoform 2 and isoform 3 are expressed in malignant Hodgkin lymphoma cells called Hodgkin and Reed-Sternberg (HRS) cells.

Molecular Interaction Atlas (MIA) of This DOT

11 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 Lymphocyte antigen 75 (LY75).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Lymphocyte antigen 75 (LY75).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Lymphocyte antigen 75 (LY75).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lymphocyte antigen 75 (LY75).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Lymphocyte antigen 75 (LY75).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Lymphocyte antigen 75 (LY75).	[6]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of Lymphocyte antigen 75 (LY75).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Lymphocyte antigen 75 (LY75).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lymphocyte antigen 75 (LY75).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lymphocyte antigen 75 (LY75).	[9]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Lymphocyte antigen 75 (LY75).	[10]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [7] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
• [8] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Cordycepin inhibits the proliferation and progression of NPC by targeting the MAPK/ERK and -catenin pathways. Oncol Lett. 2022 Jan;23(1):20. doi: 10.3892/ol.2021.13138. Epub 2021 Nov 16.