Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZHN1XQ)

• DOT Name: Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1)
• Synonyms: CD163 antigen-like 1; CD antigen CD163b
• Gene Name: CD163L1
• Related Disease:
  Melanoma
  Schizophrenia
• UniProt ID: C163B_HUMAN
• PDB ID: 6K0O
• Pfam ID: PF00530
• Sequence:
  MMLPQNSWHIDFGRCCCHQNLFSAVVTCILLLNSCFLISSFNGTDLELRLVNGDGPCSGT
  VEVKFQGQWGTVCDDGWNTTASTVVCKQLGCPFSFAMFRFGQAVTRHGKIWLDDVSCYGN
  ESALWECQHREWGSHNCYHGEDVGVNCYGEANLGLRLVDGNNSCSGRVEVKFQERWGTIC
  DDGWNLNTAAVVCRQLGCPSSFISSGVVNSPAVLRPIWLDDILCQGNELALWNCRHRGWG
  NHDCSHNEDVTLTCYDSSDLELRLVGGTNRCMGRVELKIQGRWGTVCHHKWNNAAADVVC
  KQLGCGTALHFAGLPHLQSGSDVVWLDGVSCSGNESFLWDCRHSGTVNFDCLHQNDVSVI
  CSDGADLELRLADGSNNCSGRVEVRIHEQWWTICDQNWKNEQALVVCKQLGCPFSVFGSR
  RAKPSNEARDIWINSISCTGNESALWDCTYDGKAKRTCFRRSDAGVICSDKADLDLRLVG
  AHSPCYGRLEVKYQGEWGTVCHDRWSTRNAAVVCKQLGCGKPLHVFGMTYFKEASGPIWL
  DDVSCIGNESNIWDCEHSGWGKHNCVHREDVIVTCSGDATWGLRLVGGSNRCSGRLEVYF
  QGRWGTVCDDGWNSKAAAVVCSQLDCPSSIIGMGLGNASTGYGKIWLDDVSCDGDESDLW
  SCRNSGWGNNDCSHSEDVGVICSDASDMELRLVGGSSRCAGKVEVNVQGAVGILCANGWG
  MNIAEVVCRQLECGSAIRVSREPHFTERTLHILMSNSGCTGGEASLWDCIRWEWKQTACH
  LNMEASLICSAHRQPRLVGADMPCSGRVEVKHADTWRSVCDSDFSLHAANVLCRELNCGD
  AISLSVGDHFGKGNGLTWAEKFQCEGSETHLALCPIVQHPEDTCIHSREVGVVCSRYTDV
  RLVNGKSQCDGQVEINVLGHWGSLCDTHWDPEDARVLCRQLSCGTALSTTGGKYIGERSV
  RVWGHRFHCLGNESLLDNCQMTVLGAPPCIHGNTVSVICTGSLTQPLFPCLANVSDPYLS
  AVPEGSALICLEDKRLRLVDGDSRCAGRVEIYHDGFWGTICDDGWDLSDAHVVCQKLGCG
  VAFNATVSAHFGEGSGPIWLDDLNCTGMESHLWQCPSRGWGQHDCRHKEDAGVICSEFTA
  LRLYSETETESCAGRLEVFYNGTWGSVGRRNITTAIAGIVCRQLGCGENGVVSLAPLSKT
  GSGFMWVDDIQCPKTHISIWQCLSAPWERRISSPAEETWITCEDRIRVRGGDTECSGRVE
  IWHAGSWGTVCDDSWDLAEAEVVCQQLGCGSALAALRDASFGQGTGTIWLDDMRCKGNES
  FLWDCHAKPWGQSDCGHKEDAGVRCSGQSLKSLNASSGHLALILSSIFGLLLLVLFILFL
  TWCRVQKQKHLPLRVSTRRRGSLEENLFHEMETCLKREDPHGTRTSDDTPNHGCEDASDT
  SLLGVLPASEATK
• Tissue Specificity: Isoform 1 is highly expressed in the spleen, lymph nodes, thymus, and fetal liver and weakly expressed in bone marrow and no expression was found in peripheral blood leukocytes. Isoform 1 expression is restricted to the monocyte and macrophage cell lines. Isoform 2 is only expressed in spleen.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	No Known	Unknown	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[10]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[11]

6 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 Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Scavenger receptor cysteine-rich type 1 protein M160 (CD163L1).	[9]

References

• [1] Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.Nat Genet. 2012 Sep;44(9):1006-14. doi: 10.1038/ng.2359. Epub 2012 Jul 29.
• [2] De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014 Feb 13;506(7487):179-84. doi: 10.1038/nature12929. Epub 2014 Jan 22.
• [3] 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.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] 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.
• [11] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.