Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3OTNLM)

• DOT Name: F-box/LRR-repeat protein 16 (FBXL16)
• Synonyms: F-box and leucine-rich repeat protein 16
• Gene Name: FBXL16
• Related Disease: Attention deficit hyperactivity disorder
• UniProt ID: FXL16_HUMAN
• Pfam ID: PF13516
• Sequence:
  MSSPGIDGDPKPPCLPRNGLVKLPGQPNGLGAASITKGTPATKNRPCQPPPPPTLPPPSL
  AAPLSRAALAGGPCTPAGGPASALAPGHPAERPPLATDEKILNGLFWYFSACEKCVLAQV
  CKAWRRVLYQPKFWAGLTPVLHAKELYNVLPGGEKEFVNLQGFAARGFEGFCLVGVSDLD
  ICEFIDNYALSKKGVKAMSLKRSTITDAGLEVMLEQMQGVVRLELSGCNDFTEAGLWSSL
  SARITSLSVSDCINVADDAIAAISQLLPNLAELSLQAYHVTDTALAYFTARQGHSTHTLR
  LLSCWEITNHGVVNVVHSLPNLTALSLSGCSKVTDDGVELVAENLRKLRSLDLSWCPRIT
  DMALEYVACDLHRLEELVLDRCVRITDTGLSYLSTMSSLRSLYLRWCCQVQDFGLKHLLA
  LGSLRLLSLAGCPLLTTTGLSGLVQLQELEELELTNCPGATPELFKYFSQHLPRCLVIE
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of F-box/LRR-repeat protein 16 (FBXL16).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of F-box/LRR-repeat protein 16 (FBXL16).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of F-box/LRR-repeat protein 16 (FBXL16).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of F-box/LRR-repeat protein 16 (FBXL16).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of F-box/LRR-repeat protein 16 (FBXL16).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of F-box/LRR-repeat protein 16 (FBXL16).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of F-box/LRR-repeat protein 16 (FBXL16).	[4]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of F-box/LRR-repeat protein 16 (FBXL16).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of F-box/LRR-repeat protein 16 (FBXL16).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of F-box/LRR-repeat protein 16 (FBXL16).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of F-box/LRR-repeat protein 16 (FBXL16).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of F-box/LRR-repeat protein 16 (FBXL16).	[12]

References

• [1] A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder.Biol Psychiatry. 2018 Jun 15;83(12):1044-1053. doi: 10.1016/j.biopsych.2017.11.026. Epub 2017 Dec 2.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] 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.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [9] Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
• [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.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.