Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ607YT)

• DOT Name: BTB/POZ domain-containing protein 3 (BTBD3)
• Gene Name: BTBD3
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
• UniProt ID: BTBD3_HUMAN
• Pfam ID: PF07707 ; PF00651 ; PF08005
• Sequence:
  MVDDKEKNMKCLTFFLMLPETVKNRSKKSSKKANTSSSSSNSSKLPPVCYEIITLKTKKK
  KMAADIFPRKKPANSSSTSVQQYHQQNLSNNNLIPAPNWQGLYPTIRERNAMMFNNDLMA
  DVHFVVGPPGGTQRLPGHKYVLAVGSSVFHAMFYGELAEDKDEIRIPDVEPAAFLAMLKY
  IYCDEIDLAADTVLATLYAAKKYIVPHLARACVNFLETSLSAKNACVLLSQSCLFEEPDL
  TQRCWEVIDAQAELALKSEGFCDIDFQTLESILRRETLNAKEIVVFEAALNWAEVECQRQ
  DLALSIENKRKVLGKALYLIRIPTMALDDFANGAAQSGVLTLNETNDIFLWYTAAKKPEL
  QFVSKARKGLVPQRCHRFQSCAYRSNQWRYRGRCDSIQFAVDKRVFIAGFGLYGSSCGSA
  EYSAKIELKRQGVVLGQNLSKYFSDGSSNTFPVWFEYPVQIEPDTFYTASVILDGNELSY
  FGQEGMTEVQCGKVTVQFQCSSDSTNGTGVQGGQIPELIFYA
• Function: Acts as a key regulator of dendritic field orientation during development of sensory cortex. Also directs dendrites toward active axon terminals when ectopically expressed.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	BTB/POZ domain-containing protein 3 (BTBD3) affects the response to substance of Methotrexate.	[15]
Mitoxantrone	DMM39BF	Approved	BTB/POZ domain-containing protein 3 (BTBD3) affects the response to substance of Mitoxantrone.	[15]

11 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 BTB/POZ domain-containing protein 3 (BTBD3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[10]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[12]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of BTB/POZ domain-containing protein 3 (BTBD3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of BTB/POZ domain-containing protein 3 (BTBD3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of BTB/POZ domain-containing protein 3 (BTBD3).	[13]

References

• [1] Preliminary investigation of the role of BTB domain-containing 3 gene in the proliferation and metastasis of hepatocellular carcinoma.Oncol Lett. 2017 Aug;14(2):2505-2510. doi: 10.3892/ol.2017.6369. Epub 2017 Jun 9.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [6] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol. 2005 Mar;128(5):636-44.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [11] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [15] 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.