Details of Drug Off-Target (DOT)

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

• DOT Name: Oncostatin-M-specific receptor subunit beta (OSMR)
• Synonyms: Interleukin-31 receptor subunit beta; IL-31 receptor subunit beta; IL-31R subunit beta; IL-31R-beta; IL-31RB
• Gene Name: OSMR
• Related Disease:
  Amyloidosis, primary localized cutaneous, 1
  Familial primary localized cutaneous amyloidosis
• UniProt ID: OSMR_HUMAN
• Pfam ID: PF00041 ; PF21177 ; PF17971
• Sequence:
  MALFAVFQTTFFLTLLSLRTYQSEVLAERLPLTPVSLKVSTNSTRQSLHLQWTVHNLPYH
  QELKMVFQIQISRIETSNVIWVGNYSTTVKWNQVLHWSWESELPLECATHFVRIKSLVDD
  AKFPEPNFWSNWSSWEEVSVQDSTGQDILFVFPKDKLVEEGTNVTICYVSRNIQNNVSCY
  LEGKQIHGEQLDPHVTAFNLNSVPFIRNKGTNIYCEASQGNVSEGMKGIVLFVSKVLEEP
  KDFSCETEDFKTLHCTWDPGTDTALGWSKQPSQSYTLFESFSGEKKLCTHKNWCNWQITQ
  DSQETYNFTLIAENYLRKRSVNILFNLTHRVYLMNPFSVNFENVNATNAIMTWKVHSIRN
  NFTYLCQIELHGEGKMMQYNVSIKVNGEYFLSELEPATEYMARVRCADASHFWKWSEWSG
  QNFTTLEAAPSEAPDVWRIVSLEPGNHTVTLFWKPLSKLHANGKILFYNVVVENLDKPSS
  SELHSIPAPANSTKLILDRCSYQICVIANNSVGASPASVIVISADPENKEVEEERIAGTE
  GGFSLSWKPQPGDVIGYVVDWCDHTQDVLGDFQWKNVGPNTTSTVISTDAFRPGVRYDFR
  IYGLSTKRIACLLEKKTGYSQELAPSDNPHVLVDTLTSHSFTLSWKDYSTESQPGFIQGY
  HVYLKSKARQCHPRFEKAVLSDGSECCKYKIDNPEEKALIVDNLKPESFYEFFITPFTSA
  GEGPSATFTKVTTPDEHSSMLIHILLPMVFCVLLIMVMCYLKSQWIKETCYPDIPDPYKS
  SILSLIKFKENPHLIIMNVSDCIPDAIEVVSKPEGTKIQFLGTRKSLTETELTKPNYLYL
  LPTEKNHSGPGPCICFENLTYNQAASDSGSCGHVPVSPKAPSMLGLMTSPENVLKALEKN
  YMNSLGEIPAGETSLNYVSQLASPMFGDKDSLPTNPVEAPHCSEYKMQMAVSLRLALPPP
  TENSSLSSITLLDPGEHYC
• Function: Associates with IL31RA to form the IL31 receptor. Binds IL31 to activate STAT3 and possibly STAT1 and STAT5. Capable of transducing OSM-specific signaling events.
• Tissue Specificity: Expressed in keratinocytes (at protein level) . Expressed at relatively high levels in all neural cells as well as fibroblast and epithelial cells .
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: IL-6-type cytokine receptor ligand interactions (R-HSA-6788467)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyloidosis, primary localized cutaneous, 1	DISKTUHS	Strong	Autosomal dominant	[1]
Familial primary localized cutaneous amyloidosis	DISDIR8A	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Oncostatin-M-specific receptor subunit beta (OSMR) increases the response to substance of Paclitaxel.	[17]
Gefitinib	DM15F0X	Approved	Oncostatin-M-specific receptor subunit beta (OSMR) affects the response to substance of Gefitinib.	[18]

13 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 Oncostatin-M-specific receptor subunit beta (OSMR).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[8]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[15]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Oncostatin-M-specific receptor subunit beta (OSMR).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Oncostatin-M-specific receptor subunit beta (OSMR).	[13]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] The molecular skin pathology of familial primary localized cutaneous amyloidosis. Exp Dermatol. 2010 May;19(5):416-23. doi: 10.1111/j.1600-0625.2010.01083.x.
• [3] 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.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [9] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [17] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
• [18] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.