Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY0B5TX)

• DOT Name: F-box/LRR-repeat protein 8 (FBXL8)
• Synonyms: F-box and leucine-rich repeat protein 8; F-box protein FBL8
• Gene Name: FBXL8
• UniProt ID: FBXL8_HUMAN
• Pfam ID: PF12937
• Sequence:
  MAEPGEGLPEEVLALIFRHLSLRDRAAAARVCRAWAAAATCSAVWHDTKISCECELEGML
  PPYLSACLDHIHNLRLEFEPSRKPSRRAAIELLMVLAGRAPGLRGLRLECRGEKPLFDAG
  RDVLEAVHAVCGAASQLRHLDLRRLSFTLDDALVLQAARSCPELHSLFLDNSTLVGSVGP
  GSVLELLEACPRLRALGLHLASLSHAILEALAAPDRAPFALLALRCACPEDARASPLPNE
  AWVALRRRHPGLAVELELEPALPAESVTRVLQPAVPVAALRLNLSGDTVGPVRFAAHHYA
  ATLCALEVRAAASAELNAALEELAARCAALREVHCFCVVSHSVLDAFRAHCPRLRTYTLK
  LTREPHPWRPTLVA
• Function: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of F-box/LRR-repeat protein 8 (FBXL8).	[1]
Selenium	DM25CGV	Approved	Selenium increases the expression of F-box/LRR-repeat protein 8 (FBXL8).	[2]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of F-box/LRR-repeat protein 8 (FBXL8).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of F-box/LRR-repeat protein 8 (FBXL8).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of F-box/LRR-repeat protein 8 (FBXL8).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of F-box/LRR-repeat protein 8 (FBXL8).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of F-box/LRR-repeat protein 8 (FBXL8).	[6]

References

• [1] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [2] 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.
• [3] The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
• [4] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [5] 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.
• [6] 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.
• [7] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.