Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBN6ZUC)

• DOT Name: BTB/POZ domain-containing protein KCTD9 (KCTD9)
• Gene Name: KCTD9
• Related Disease:
  Acute liver failure
  Chronic hepatitis B virus infection
  Hepatitis B virus infection
• UniProt ID: KCTD9_HUMAN
• PDB ID: 5BXH
• Pfam ID: PF02214 ; PF11834 ; PF00805
• Sequence:
  MRRVTLFLNGSPKNGKVVAVYGTLSDLLSVASSKLGIKATSVYNGKGGLIDDIALIRDDD
  VLFVCEGEPFIDPQTDSKPPEGLLGFHTDWLTLNVGGRYFTTTRSTLVNKEPDSMLAHMF
  KDKGVWGNKQDHRGAFLIDRSPEYFEPILNYLRHGQLIVNDGINLLGVLEEARFFGIDSL
  IEHLEVAIKNSQPPEDHSPISRKEFVRFLLATPTKSELRCQGLNFSGADLSRLDLRYINF
  KMANLSRCNLAHANLCCANLERADLSGSVLDCANLQGVKMLCSNAEGASLKLCNFEDPSG
  LKANLEGANLKGVDMEGSQMTGINLRVATLKNAKLKNCNLRGATLAGTDLENCDLSGCDL
  QEANLRGSNVKGAIFEEMLTPLHMSQSVR
• Function: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of target proteins, leading to their degradation by the proteasome.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute liver failure	DIS5EZKX	Strong	Biomarker	[1]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Biomarker	[2]
Hepatitis B virus infection	DISLQ2XY	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[7]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[10]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of BTB/POZ domain-containing protein KCTD9 (KCTD9).	[11]

References

• [1] Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice.BMC Immunol. 2018 Jun 25;19(1):20. doi: 10.1186/s12865-018-0256-x.
• [2] KCTD9 contributes to liver injury through NK cell activation during hepatitis B virus-induced acute-on-chronic liver failure.Clin Immunol. 2013 Mar;146(3):207-16. doi: 10.1016/j.clim.2012.12.013. Epub 2013 Jan 7.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [6] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [7] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [8] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.