Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5UVB1J)

• DOT Name: Cerebellar degeneration-related protein 2-like (CDR2L)
• Synonyms: Paraneoplastic 62 kDa antigen
• Gene Name: CDR2L
• Related Disease:
  Cerebellar degeneration
  Neoplasm
• UniProt ID: CDR2L_HUMAN
• Sequence:
  MRRAAGMEDFSAEEEESWYDQQDLEQDLHLAAELGKTLLERNKELEGSLQQMYSTNEEQV
  QEIEYLTKQLDTLRHVNEQHAKVYEQLDLTARDLELTNHRLVLESKAAQQKIHGLTETIE
  RLQAQVEELQAQVEQLRGLEQLRVLREKRERRRTIHTFPCLKELCTSPRCKDAFRLHSSS
  LELGPRPLEQENERLQTLVGALRSQVSQERQRKERAEREYTAVLQEYSELERQLCEMEAC
  RLRVQELEAELLELQQMKQAKTYLLGPDDHLAEALLAPLTQAPEADDPQPGRGDDLGAQD
  GVSSPAASPGHVVRKSCSDTALNAIVAKDPASRHAGNLTLHANSVRKRGMSILREVDEQY
  HALLEKYEELLSKCRQHGAGVRHAGVQTSRPISRDSSWRDLRGGEEGQGEVKAGEKSLSQ
  HVEAVDKRLEQSQPEYKALFKEIFSRIQKTKADINATKVKTHSSK

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebellar degeneration	DISPBCM3	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cerebellar degeneration-related protein 2-like (CDR2L).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cerebellar degeneration-related protein 2-like (CDR2L).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cerebellar degeneration-related protein 2-like (CDR2L).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Cerebellar degeneration-related protein 2-like (CDR2L).	[15]

10 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 Cerebellar degeneration-related protein 2-like (CDR2L).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[13]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Cerebellar degeneration-related protein 2-like (CDR2L).	[10]

References

• [1] Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity.Neuropathol Appl Neurobiol. 2019 Feb;45(2):141-156. doi: 10.1111/nan.12492. Epub 2018 May 24.
• [2] Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration.Acta Neuropathol. 2018 Apr;135(4):569-579. doi: 10.1007/s00401-017-1802-y. Epub 2018 Jan 3.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] 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.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [10] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] 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.