Details of Drug Off-Target (DOT)

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

• DOT Name: Kelch domain-containing protein 9 (KLHDC9)
• Synonyms: Kelch/ankyrin repeat-containing cyclin A1-interacting protein
• Gene Name: KLHDC9
• UniProt ID: KLDC9_HUMAN
• Pfam ID: PF13415
• Sequence:
  MAVAVPPGRAAGSGWAWRPVARDALLARAFHSCTELRGRFYLVGGLLAGGAREPSSDTVV
  FDPARGQAVRLGARGSPPRSHHDAAPVDGRWLCVVGGWDGSRRLATVTALDTERGVWEAW
  TGTPGDCPPAGLSSHTCTRISDRELQVAGREGGIHTQRRYGSIYTLRLDPSARTYCYKQE
  GCHTASRSGHCAALLQTPGPHPGHQLLLFGGCNLAEPEVAGHWSHGKIKEEPPVAPHLME
  QLARLVSSGQGSQKGPHGLRHHSCSVVGPFAVLFGGETLTRARDTICNDLYIYDTRTSPP
  LWFHFPCADRGMKRMGHRTCLWNDQLYLVGGFGEDGRTASPQVCILDFI

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Kelch domain-containing protein 9 (KLHDC9).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Kelch domain-containing protein 9 (KLHDC9).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kelch domain-containing protein 9 (KLHDC9).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Kelch domain-containing protein 9 (KLHDC9).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Kelch domain-containing protein 9 (KLHDC9).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Kelch domain-containing protein 9 (KLHDC9).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kelch domain-containing protein 9 (KLHDC9).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Kelch domain-containing protein 9 (KLHDC9).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Kelch domain-containing protein 9 (KLHDC9).	[10]

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 decreases the methylation of Kelch domain-containing protein 9 (KLHDC9).	[9]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [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] 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.