Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3MW415)

• DOT Name: Ankyrin repeat domain-containing protein 36B (ANKRD36B)
• Synonyms: CLL-associated antigen KW-1
• Gene Name: ANKRD36B
• Related Disease:
  Melanoma
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Bladder cancer
  Carcinoma of esophagus
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Immunodeficiency
  Laryngeal carcinoma
  Laryngeal disorder
  Laryngeal squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm of esophagus
  Sarcoma
  Soft tissue sarcoma
  Squamous cell carcinoma
  Testicular cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Urothelial carcinoma
  Carcinoma
  Pancreatic cancer
  Prader-Willi syndrome
  Synovial sarcoma
  Triple negative breast cancer
  Uveal Melanoma
  Breast cancer
  Breast carcinoma
  Cutaneous squamous cell carcinoma
  Stomach cancer
  Thyroid gland papillary carcinoma
• UniProt ID: AN36B_HUMAN
• Pfam ID: PF12796 ; PF14915
• Sequence:
  MERLCSDGFAFPHYYIKPYHLKRIHRAVLRGNLEKLKYLLLTYYDANKRDRKERTALHLA
  CATGQPEMVHLLVSRRCELNLCDREDRTPLIKAVQLRQEACATLLLQNGADPNITDVFGR
  TALHYAVYNEDTSMIEKLLSHGTNIEECSKNEYQPLLLAVSRRKVKMVEFLLKKKANVNA
  IDYLGRSALILAVTLGEKDIVILLLQHNIDVFSRDVYGKLAEDYASEAENRVIFDLIYEY
  KRKRYEDLPINSNPVSPQKQRAEKATSDDKDSVSNIATEIKEGPISGTVSSQKQPAEKAT
  SDEKDSVSNIATEIKEGQQSGTVSPQKQSAQKVIFKKKVSLLNIATRIMGGGKSGTVSSQ
  KQPASKTASDKTDSALNTATEIKDGLQCGTVSSQKQQALKATTDEEGSVSNIATEIKDGE
  KSGTVSSQKKPALKATSDEKDSFSNITREKKDGEISRTVSSQKPPALKATSVKEDSVLNI
  AREKKDGEKSRTVSFEQPPGLKATRDEKDSLLNIARGKKDGEKTRRVSSHKQPSLKATSD
  KEDSVPNMATETKDEQISGTVSCQKQPALKATSDKKDSVSNIPTEIKDGQQSGTVSSQKQ
  PAWKATSVKKDSVSNIATEIKDGQIRGTVSSQRRPALKTTGDEKDSVSNIAREIKDGEKS
  GTVSPQKQSAQKVIFKKKVSLLNIATRITGGGKSGTEYPENLRTLKATIENKDSVLNTAT
  KMKEVQTSTPAEQDLEMASEGEQKRLEEYENNQPQVKNQIHSRDDLDDIIQSSQTVSEDG
  DSLCCNCKNVILLIDQHEMKCKDCVHLLKIKNTFCLWKRLIKLKDNHCEQLRVKIRKLKN
  KASVLQKRISEKEEIKSQLKHEILELEKELCSLRFAIQQEKKKRRNVEELHQKVREKLRI
  TEEQYRIEADVTKPIKPALKSAEVELKTGGNNSNQVSETDEKEDLLHENRLMQDEIARLR
  LEKDTIKNQNLEKKYLKDFEIVKRKHEDLQKALKRNGETLAKTIACYSGQLAALTDENTT
  LRSKLEKQRESRQRLETEMQSYRCRLNAARCDHDQSHSSKRDQELAFQGTVDKCRHLQEN
  LNSHVLILSLQLSKAESKSRVLKTELHYTGEALKEKALVFEHVQSELKQKQSQMKDIEKM
  YKSGYNTMEKCIEKQERFCQLKKQNMLLQQQLDDARNKADNQEKAILNIQARCDARVQNL
  QAECRKHRLLLEEDNKMLVNELNHSKEKECQYEKEKAEREVAVRQLQQKRDDVLNKGSAT
  KALLDASSRHCTYLENGMQDSRKKLDQMRSQFQEIQDQLTATIRCTKEMEGDTQKLEVEH
  VMMRKIIKKQDDQIERLEKILQHSSLMLQVFES

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[9]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[12]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[13]
Immunodeficiency	DIS093I0	Strong	Altered Expression	[14]
Laryngeal carcinoma	DISNHCIV	Strong	Altered Expression	[15]
Laryngeal disorder	DISDKUQO	Strong	Altered Expression	[13]
Laryngeal squamous cell carcinoma	DIS9UUVF	Strong	Biomarker	[16]
Lung cancer	DISCM4YA	Strong	Altered Expression	[17]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[17]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[6]
Sarcoma	DISZDG3U	Strong	Biomarker	[18]
Soft tissue sarcoma	DISSN8XB	Strong	Biomarker	[18]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[2]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[18]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[19]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[19]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[19]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[20]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[5]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[20]
Carcinoma	DISH9F1N	moderate	Altered Expression	[21]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[22]
Prader-Willi syndrome	DISYWMLU	moderate	Genetic Variation	[23]
Synovial sarcoma	DISEZJS7	moderate	Biomarker	[18]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[24]
Uveal Melanoma	DISA7ZGL	moderate	Biomarker	[25]
Breast cancer	DIS7DPX1	Limited	Biomarker	[26]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[26]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[27]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[10]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[28]

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 Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[34]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[35]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[36]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[29]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[38]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Ankyrin repeat domain-containing protein 36B (ANKRD36B).	[30]

References

• [1] Recombinant DNA technology for melanoma immunotherapy: anti-Id DNA vaccines targeting high molecular weight melanoma-associated antigen.Mol Biotechnol. 2014 Nov;56(11):1032-9. doi: 10.1007/s12033-014-9782-9.
• [2] Gene expression of MAGE-A3 and PRAME tumor antigens and EGFR mutational status in Taiwanese non-small cell lung cancer patients.Asia Pac J Clin Oncol. 2017 Oct;13(5):e212-e223. doi: 10.1111/ajco.12586. Epub 2016 Aug 12.
• [3] A DNA vaccine expressing tyrosinase-related protein-2 induces T-cell-mediated protection against mouse glioblastoma.Cancer Gene Ther. 2003 Sep;10(9):678-88. doi: 10.1038/sj.cgt.7700620.
• [4] Cancer-testis antigens MAGEA proteins are incorporated into extracellular vesicles released by cells.Oncotarget. 2019 Jun 4;10(38):3694-3708. doi: 10.18632/oncotarget.26979. eCollection 2019 Jun 4.
• [5] Multitarget fluorescence in situ hybridization and melanoma antigen genes analysis in primary bladder carcinoma.Cancer Genet Cytogenet. 2006 Jan 1;164(1):32-8. doi: 10.1016/j.cancergencyto.2005.06.006.
• [6] Demethylation-mediated upregulation of melanoma-associated antigen-A11 correlates with malignant progression of esophageal squamous cell carcinoma.Dig Liver Dis. 2019 Oct;51(10):1475-1482. doi: 10.1016/j.dld.2019.04.018. Epub 2019 May 31.
• [7] The expression of MAGE and SSX, and correlation of COX2, VEGF, and survivin in colorectal cancer.Anticancer Res. 2012 Feb;32(2):559-64.
• [8] The Expression of Melanoma-Associated Antigen D2 Both in Surgically Resected and Serum Samples Serves as Clinically Relevant Biomarker of Gastric Cancer Progression.Ann Surg Oncol. 2016 Feb;23 Suppl 2:S214-21. doi: 10.1245/s10434-015-4457-8. Epub 2015 Mar 6.
• [9] Expression, Function, and Prognostic Value of MAGE-D4 Protein in Esophageal Squamous Cell Carcinoma.Anticancer Res. 2019 Nov;39(11):6015-6023. doi: 10.21873/anticanres.13807.
• [10] Tissue Expression of Melanoma-associated Antigen A6 and Clinical Characteristics of Gastric Cancer.Anticancer Res. 2019 Nov;39(11):5903-5910. doi: 10.21873/anticanres.13794.
• [11] Melanoma-associated antigen A2 is overexpressed in glioma and associated with poor prognosis in glioma patients.Neoplasma. 2018;65(4):604-609. doi: 10.4149/neo_2018_170625N440.
• [12] Melanoma-associated antigen A11 reduces erlotinib and afatinib efficacy in head and neck cancer.J Craniomaxillofac Surg. 2018 Mar;46(3):492-497. doi: 10.1016/j.jcms.2017.12.014. Epub 2017 Dec 24.
• [13] Clinical significance of melanoma-associated antigen A1-6 expression in sputum of patients with squamous cell carcinoma of the larynx and hypopharynx.Head Neck. 2016 Apr;38 Suppl 1:E736-40. doi: 10.1002/hed.24081. Epub 2015 Jul 18.
• [14] T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/cnull mice.Cancer Sci. 2012 Jan;103(1):17-25. doi: 10.1111/j.1349-7006.2011.02111.x. Epub 2011 Nov 8.
• [15] Expression and prognostic value of MAGE-A9 in laryngeal squamous cell carcinoma.Int J Clin Exp Pathol. 2014 Sep 15;7(10):6734-42. eCollection 2014.
• [16] MiR-143-3p suppresses cell proliferation, migration, and invasion by targeting Melanoma-Associated Antigen A9 in laryngeal squamous cell carcinoma.J Cell Biochem. 2019 Feb;120(2):1245-1257. doi: 10.1002/jcb.27084. Epub 2018 Oct 9.
• [17] Association of MAGE A1-6 Expression with Lung Cancer Progression.J Cancer. 2017 May 12;8(8):1324-1329. doi: 10.7150/jca.18086. eCollection 2017.
• [18] Immunohistochemical expression and clinicopathological assessment of the cancer testis antigens NY-ESO-1 and MAGE-A4 in high-grade soft-tissue sarcoma.Oncol Lett. 2019 Apr;17(4):3937-3943. doi: 10.3892/ol.2019.10044. Epub 2019 Feb 14.
• [19] The cancer/testis antigen melanoma-associated antigen-A3/A6 is a novel target of fibroblast growth factor receptor 2-IIIb through histone H3 modifications in thyroid cancer.Clin Cancer Res. 2007 Aug 15;13(16):4713-20. doi: 10.1158/1078-0432.CCR-07-0618.
• [20] Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma.Cancer Immunol Immunother. 2019 May;68(5):743-751. doi: 10.1007/s00262-019-02316-w. Epub 2019 Feb 21.
• [21] Clinical application of MAGE A1-6 RT-nested PCR for diagnosis of lung cancer invisible by bronchoscopy.Anticancer Res. 2012 Jan;32(1):163-7.
• [22] Functional and mechanistic studies reveal MAGEA3 as a pro-survival factor in pancreatic cancer cells.J Exp Clin Cancer Res. 2019 Jul 8;38(1):294. doi: 10.1186/s13046-019-1272-2.
• [23] Necdin protects embryonic motoneurons from programmed cell death.PLoS One. 2011;6(9):e23764. doi: 10.1371/journal.pone.0023764. Epub 2011 Sep 2.
• [24] hMAGEA2 promotes progression of breast cancer by regulating Akt and Erk1/2 pathways.Oncotarget. 2017 Jun 6;8(23):37115-37127. doi: 10.18632/oncotarget.16184.
• [25] An ocular melanoma-associated antigen. Molecular characterization.Arch Ophthalmol. 1992 Mar;110(3):399-404. doi: 10.1001/archopht.1992.01080150097036.
• [26] Prognostic roles of MAGE family members in breast cancer based on KM-Plotter Data.Oncol Lett. 2019 Oct;18(4):3501-3516. doi: 10.3892/ol.2019.10722. Epub 2019 Aug 6.
• [27] Overexpression and Implications of Melanoma-associated Antigen A12 in Pathogenesis of Human Cutaneous Squamous Cell Carcinoma.Anticancer Res. 2019 Apr;39(4):1849-1857. doi: 10.21873/anticanres.13292.
• [28] Expression of MAGE A1-6 and the clinical characteristics of papillary thyroid carcinoma.Anticancer Res. 2013 Apr;33(4):1731-5.
• [29] 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.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [34] 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.
• [35] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [36] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [37] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [38] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.
• [39] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.