Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVTR1KY)

• DOT Name: F-box/LRR-repeat protein 20 (FBXL20)
• Synonyms: F-box and leucine-rich repeat protein 20; F-box/LRR-repeat protein 2-like
• Gene Name: FBXL20
• Related Disease:
  Asthma
  Colon carcinoma
  Colorectal adenocarcinoma
  Primary biliary cholangitis
  Chronic kidney disease
• UniProt ID: FXL20_HUMAN
• Pfam ID: PF12937 ; PF13516
• Sequence:
  MRRDVNGVTKSRFEMFSNSDEAVINKKLPKELLLRIFSFLDVVTLCRCAQVSRAWNVLAL
  DGSNWQRIDLFDFQRDIEGRVVENISKRCGGFLRKLSLRGCLGVGDNALRTFAQNCRNIE
  VLNLNGCTKTTDATCTSLSKFCSKLRHLDLASCTSITNMSLKALSEGCPLLEQLNISWCD
  QVTKDGIQALVRGCGGLKALFLKGCTQLEDEALKYIGAHCPELVTLNLQTCLQITDEGLI
  TICRGCHKLQSLCASGCSNITDAILNALGQNCPRLRILEVARCSQLTDVGFTTLARNCHE
  LEKMDLEECVQITDSTLIQLSIHCPRLQVLSLSHCELITDDGIRHLGNGACAHDQLEVIE
  LDNCPLITDASLEHLKSCHSLERIELYDCQQITRAGIKRLRTHLPNIKVHAYFAPVTPPP
  SVGGSRQRFCRCCIIL
• Function: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Role in neural transmission.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Strong	Genetic Variation	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Colorectal adenocarcinoma	DISPQOUB	Strong	Biomarker	[2]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[3]
Chronic kidney disease	DISW82R7	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of F-box/LRR-repeat protein 20 (FBXL20).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[12]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[21]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of F-box/LRR-repeat protein 20 (FBXL20).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of F-box/LRR-repeat protein 20 (FBXL20).	[18]

References

• [1] Shared genetics of asthma and mental health disorders: a large-scale genome-wide cross-trait analysis.Eur Respir J. 2019 Dec 19;54(6):1901507. doi: 10.1183/13993003.01507-2019. Print 2019 Dec.
• [2] Role of FBXL20 in human colorectal adenocarcinoma.Oncol Rep. 2012 Dec;28(6):2290-8. doi: 10.3892/or.2012.2065. Epub 2012 Sep 27.
• [3] Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.Nat Genet. 2011 Mar 13;43(4):329-32. doi: 10.1038/ng.789.
• [4] Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.PLoS Genet. 2011 Sep;7(9):e1002264. doi: 10.1371/journal.pgen.1002264. Epub 2011 Sep 8.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] 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.
• [10] 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.
• [11] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [19] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [20] 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.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.