Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJLJ65L)

• DOT Name: Protein BCAP (ODF2L)
• Synonyms: Basal body centriole-associated protein; Outer dense fiber protein 2-like; ODF2-like protein
• Gene Name: ODF2L
• Related Disease:
  Allergic rhinitis
  Malignant soft tissue neoplasm
  Sarcoma
• UniProt ID: ODF2L_HUMAN
• Sequence:
  MEKAVNDGSHSEELFCHLKTISEKEDLPRCTSESHLSCLKQDILNEKTELEATLKEAELV
  THSVELLLPLFKDTIEKINFENANLSALNLKISEQKEILIKELDTFKSVKLALEHLLRKR
  DYKQTGDNLSSMLLENLTDNESENTNLKKKVFEKEAHIQELSCLFQSEKANTLKANRFSQ
  SVKVVHERLQIQIHKREAENDKLKEYVKSLETKIAKWNLQSRMNKNEAIVMKEASRQKTV
  ALKKASKVYKQRLDHFTGAIEKLTSQIRDQEAKLSETISASNAWKSHYEKIVIEKTELEV
  QIETMKKQIINLLEDLKKMEDHGKNSCEEILRKVHSIEYENETLNLENTKLKLRFPCRIT
  ESKNMNILIVLDMLCYISSEKTTLAALKDEVVSVENELSELQEVEKKQKTLIEMYKTQVQ
  KLQEAAEIVKSRCENLLHKNNQITKTKNKNVEKMRGQMESHLKELERVCDSLTAAERRLH
  ECQESLQCCKGKCADQEHTIRELQGQVDGNHNLLTKLSLEEENCLIQLKCENLQQKLEQM
  DAENKELEKKLANQEECLKHSNLKFKEKSAEYTALARQLEAALEEGRQKVAEEIEKMSSR
  ESALQIKILDLETELRKKNEEQNQLVCKMNSDPETP
• Function: Acts as a suppressor of ciliogenesis, specifically, the initiation of ciliogenesis.
• Tissue Specificity: Mainly expressed in trachea and testis. Not detected in bone marrow, bladder, leukocytes. Only weakly detected in tongue, stomach, brain and ovaries.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[1]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[2]
Sarcoma	DISZDG3U	Strong	Biomarker	[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 Protein BCAP (ODF2L).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein BCAP (ODF2L).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Protein BCAP (ODF2L).	[13]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein BCAP (ODF2L).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein BCAP (ODF2L).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein BCAP (ODF2L).	[6]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Protein BCAP (ODF2L).	[7]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Protein BCAP (ODF2L).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein BCAP (ODF2L).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein BCAP (ODF2L).	[11]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Protein BCAP (ODF2L).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein BCAP (ODF2L).	[14]

References

• [1] Genome-wide association study for atopy and allergic rhinitis in a Singapore Chinese population.PLoS One. 2011;6(5):e19719. doi: 10.1371/journal.pone.0019719. Epub 2011 May 20.
• [2] Anti-tumor and immunomodulatory activities induced by an alkali-extracted polysaccharide BCAP-1 from Bupleurum chinense via NF-B signaling pathway.Int J Biol Macromol. 2017 Feb;95:357-362. doi: 10.1016/j.ijbiomac.2016.10.112. Epub 2016 Nov 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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] 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.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [13] 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.
• [14] 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.