Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9NFSFI)

• DOT Name: F-box/LRR-repeat protein 6 (FBXL6)
• Synonyms: F-box and leucine-rich repeat protein 6; F-box protein FBL6; FBL6A
• Gene Name: FBXL6
• UniProt ID: FBXL6_HUMAN
• Pfam ID: PF12937
• Sequence:
  MAAPASRQVRRRARAAPRPRSAEDWWWDRLAPRGSGYHLLQSDSMLLVLSEPGPARPRAQ
  RRASRRTPRQPPRGPSAAAKPKAGLRSEAAAAPAPAPAPTPTPEEGPDAGWGDRIPLEIL
  VQIFGLLVAADGPMPFLGRAARVCRRWQEAASQPALWHTVTLSSPLVGRPAKGGVKAEKK
  LLASLEWLMPNRFSQLQRLTLIHWKSQVHPVLKLVGECCPRLTFLKLSGCHGVTADALVM
  LAKACCQLHSLDLQHSMVESTAVVSFLEEAGSRMRKLWLTYSSQTTAILGALLGSCCPQL
  QVLEVSTGINRNSIPLQLPVEALQKGCPQLQVLRLLNLMWLPKPPGRGVAPGPGFPSLEE
  LCLASSTCNFVSNEVLGRLLHGSPNLRLLDLRGCARITPAGLQDLPCRELEQLHLGLYGT
  SDRLTLAKEGSPFLTQKWCHTLRELDLSGQGFSEKDLEQALAAFLSTPGGSHPALCSLNL
  RGTRVTPSTVSSVISGCPGLLYLNLESCRCLPRGLKRAYRGLEEVQWCLEQLLTSPSPS
• Function: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

Molecular Interaction Atlas (MIA) of This DOT

2 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 6 (FBXL6).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of F-box/LRR-repeat protein 6 (FBXL6).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of F-box/LRR-repeat protein 6 (FBXL6).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of F-box/LRR-repeat protein 6 (FBXL6).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of F-box/LRR-repeat protein 6 (FBXL6).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of F-box/LRR-repeat protein 6 (FBXL6).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of F-box/LRR-repeat protein 6 (FBXL6).	[7]

References

• [1] 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.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.