Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT78IYPF)

• DOT Name: Protein bicaudal D homolog 1 (BICD1)
• Synonyms: Bic-D 1
• Gene Name: BICD1
• Related Disease:
  Aortic aneurysm
  Pancreatic cancer
  Pulmonary emphysema
  Spinal muscular atrophy
  Chronic obstructive pulmonary disease
• UniProt ID: BICD1_HUMAN
• Pfam ID: PF09730
• Sequence:
  MAAEEVLQTVDHYKTEIERLTKELTETTHEKIQAAEYGLVVLEEKLTLKQQYDELEAEYD
  SLKQELEQLKEAFGQSFSIHRKVAEDGETREETLLQESASKEAYYLGKILEMQNELKQSR
  AVVTNVQAENERLTAVVQDLKENNEMVELQRIRMKDEIREYKFREARLLQDYTELEEENI
  TLQKLVSTLKQNQVEYEGLKHEIKRFEEETVLLNSQLEDAIRLKEIAEHQLEEALETLKN
  EREQKNNLRKELSQYISLNDNHISISVDGLKFAEDGSEPNNDDKMNGHIHGPLVKLNGDY
  RTPTLRKGESLNPVSDLFSELNISEIQKLKQQLMQVEREKAILLANLQESQTQLEHTKGA
  LTEQHERVHRLTEHVNAMRGLQSSKELKAELDGEKGRDSGEEAHDYEVDINGLEILECKY
  RVAVTEVIDLKAEIKALKEKYNKSVENYTDEKAKYESKIQMYDEQVTSLEKTTKESGEKM
  AHMEKELQKMTSIANENHSTLNTAQDELVTFSEELAQLYHHVCLCNNETPNRVMLDYYRQ
  SRVTRSGSLKGPDDPRGLLSPRLARRGVSSPVETRTSSEPVAKESTEASKEPSPTKTPTI
  SPVITAPPSSPVLDTSDIRKEPMNIYNLNAIIRDQIKHLQKAVDRSLQLSRQRAAARELA
  PMIDKDKEALMEEILKLKSLLSTKREQIATLRAVLKANKQTAEVALANLKNKYENEKAMV
  TETMTKLRNELKALKEDAATFSSLRAMFATRCDEYVTQLDEMQRQLAAAEDEKKTLNTLL
  RMAIQQKLALTQRLEDLEFDHEQSRRSKGKLGKSKIGSPKVSGEASVTVPTIDTYLLHSQ
  GPQTPNIRVSSGTQRKRQFSPSLCDQSRPRTSGASYLQNLLRVPPDPTSTESFLLKGPPS
  MSEFIQGHRLSKEKRLTVAPPDCQQPAASVPPQCSQLAGRQDCPTVSPDTALPEEQPHSS
  SQCAPLHCLSKPPHP
• Function: Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport by recruiting the dynein-dynactin motor complex.
• Tissue Specificity: Expressed in the brain, heart and skeletal muscle.
• KEGG Pathway: Viral life cycle - HIV-1 (hsa03250)
• Reactome Pathway: COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aortic aneurysm	DISQ5KRA	Strong	Biomarker	[1]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[2]
Pulmonary emphysema	DIS5M7HZ	Strong	Genetic Variation	[3]
Spinal muscular atrophy	DISTLKOB	Strong	Genetic Variation	[4]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Protein bicaudal D homolog 1 (BICD1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein bicaudal D homolog 1 (BICD1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[12]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[13]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[14]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Protein bicaudal D homolog 1 (BICD1).	[15]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[16]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein bicaudal D homolog 1 (BICD1).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein bicaudal D homolog 1 (BICD1).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein bicaudal D homolog 1 (BICD1).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein bicaudal D homolog 1 (BICD1).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein bicaudal D homolog 1 (BICD1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein bicaudal D homolog 1 (BICD1).	[21]

References

• [1] Exploring the Molecular Mechanism of Thoracic Aortic Aneurysm via Bioinformatics Analysis.Med Sci Monit. 2018 Mar 14;24:1533-1539. doi: 10.12659/msm.905970.
• [2] Genome-wide association study of pancreatic cancer in Japanese population.PLoS One. 2010 Jul 29;5(7):e11824. doi: 10.1371/journal.pone.0011824.
• [3] Phenotypic and genetic heterogeneity among subjects with mild airflow obstruction in COPDGene.Respir Med. 2014 Oct;108(10):1469-80. doi: 10.1016/j.rmed.2014.07.018. Epub 2014 Aug 11.
• [4] Phenotypic extremes of BICD2-opathies: from lethal, congenital muscular atrophy with arthrogryposis to asymptomatic with subclinical features.Eur J Hum Genet. 2017 Sep;25(9):1040-1048. doi: 10.1038/ejhg.2017.98. Epub 2017 Jun 21.
• [5] Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema.Am J Respir Crit Care Med. 2011 Jan 1;183(1):43-9. doi: 10.1164/rccm.201004-0541OC. Epub 2010 Aug 13.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] 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.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [15] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [16] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [17] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [18] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [19] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.