Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT596N5E)

• DOT Name: Breast carcinoma-amplified sequence 4 (BCAS4)
• Gene Name: BCAS4
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Intellectual disability
• UniProt ID: BCAS4_HUMAN
• Sequence:
  MQRTGGGAPRPGRNHGLPGSLRQPDPVALLMLLVDADQPEPMRSGARELALFLTPEPGAE
  AKEVEETIEGMLLRLEEFCSLADLIRSDTSQILEENIPVLKAKLTEMRGIYAKVDRLEAF
  VKMVGHHVAFLEADVLQAERDHGAFPQALRRWLGSAGLPSFRNVECSGTIPARCNLRLPG
  SSDSPASASQVAGITEVTCTGARDVRAAHTV
• Tissue Specificity: Brain, thymus, spleen, kidney and placenta. Overexpressed in most breast cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Intellectual disability	DISMBNXP	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Breast carcinoma-amplified sequence 4 (BCAS4) affects the response to substance of Cisplatin.	[16]
Fluorouracil	DMUM7HZ	Approved	Breast carcinoma-amplified sequence 4 (BCAS4) affects the response to substance of Fluorouracil.	[16]

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 Breast carcinoma-amplified sequence 4 (BCAS4).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Breast carcinoma-amplified sequence 4 (BCAS4).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Breast carcinoma-amplified sequence 4 (BCAS4).	[12]

References

• [1] Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo amplification, overexpression, and fusion in breast cancer.Genes Chromosomes Cancer. 2002 Dec;35(4):311-7. doi: 10.1002/gcc.10121.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] Multigene deletions on chromosome 20q13.13-q13.2 including SALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay.Hum Mutat. 2007 Aug;28(8):830. doi: 10.1002/humu.9502.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [11] 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.
• [12] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [13] 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.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.