Details of Drug Off-Target (DOT)

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

• DOT Name: F-box only protein 16 (FBXO16)
• Gene Name: FBXO16
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Advanced cancer
  Neoplasm
• UniProt ID: FBX16_HUMAN
• Pfam ID: PF12937
• Sequence:
  MMAFAPPKNTDGPKMQTKMSTWTPLNHQLLNDRVFEERRALLGKWFDKWTDSQRRRILTG
  LLERCSLSQQKFCCRKLQEKIPAEALDFTTKLPRVLSLYIFSFLDPRSLCRCAQVCWHWK
  NLAELDQLWMLKCLRFNWYINFSPTPFEQGIWKKHYIQMVKELHITKPKTPPKDGFVIAD
  VQLVTSNSPEEKQSPLSAFRSSSSLRKKNNSGEKALPPWRSSDKHPTDIIRFNYLDNRDP
  METVQQGRRKRNQMTPDFSRQSHDKKNKLQDRTRLRKAQSMMSRRNPFPLCP
• Function: Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation.
• Tissue Specificity: Expressed in heart, spleen and colon.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of F-box only protein 16 (FBXO16).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of F-box only protein 16 (FBXO16).	[12]

11 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 only protein 16 (FBXO16).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of F-box only protein 16 (FBXO16).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of F-box only protein 16 (FBXO16).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of F-box only protein 16 (FBXO16).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of F-box only protein 16 (FBXO16).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of F-box only protein 16 (FBXO16).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of F-box only protein 16 (FBXO16).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of F-box only protein 16 (FBXO16).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of F-box only protein 16 (FBXO16).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of F-box only protein 16 (FBXO16).	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of F-box only protein 16 (FBXO16).	[15]

References

• [1] Attenuation of Tumor Suppressive Function of FBXO16 Ubiquitin Ligase Activates Wnt Signaling In Glioblastoma.Neoplasia. 2019 Jan;21(1):106-116. doi: 10.1016/j.neo.2018.11.005. Epub 2018 Dec 5.
• [2] F-box protein FBXO16 functions as a tumor suppressor by attenuating nuclear -catenin function.J Pathol. 2019 Jul;248(3):266-279. doi: 10.1002/path.5252. Epub 2019 Mar 8.
• [3] 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.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.