Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI7ZM75)

• DOT Name: Refilin-B (RFLNB)
• Synonyms: Regulator of filamin protein B; RefilinB
• Gene Name: RFLNB
• Related Disease:
  Neuroblastoma
  Cholestasis
• UniProt ID: RFLB_HUMAN
• Pfam ID: PF15068
• Sequence:
  MVGRLSLQDVPELVDAKKKGDGVLDSPDSGLPPSPSPSHWGLAAGGGGGERAAAPGTLEP
  DAAAATPAAPSPASLPLAPGCALRLCPLSFGEGVEFDPLPPKEVRYTSLVKYDSERHFID
  DVQLPLGLAVASCSQTVTCVPNGTWRNYKAEVRFEPRHRPTRFLSTTIVYPKYPKAVYTT
  TLDYNCRKTLRRFLSSVELEAAELPGSDDLSDEC
• Function: Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins. Plays an essential role in the formation of cartilaginous skeletal elements.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	moderate	Biomarker	[1]
Cholestasis	DISDJJWE	Limited	Biomarker	[2]

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 Refilin-B (RFLNB).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Refilin-B (RFLNB).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Refilin-B (RFLNB).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Refilin-B (RFLNB).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Refilin-B (RFLNB).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Refilin-B (RFLNB).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Refilin-B (RFLNB).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Refilin-B (RFLNB).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Refilin-B (RFLNB).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Refilin-B (RFLNB).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Refilin-B (RFLNB).	[10]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Refilin-B (RFLNB).	[11]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Refilin-B (RFLNB).	[12]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Refilin-B (RFLNB).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Refilin-B (RFLNB).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Refilin-B (RFLNB).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Refilin-B (RFLNB).	[17]

References

• [1] Mechanisms of neuroblastoma cell growth inhibition by CARP-1 functional mimetics.PLoS One. 2014 Jul 17;9(7):e102567. doi: 10.1371/journal.pone.0102567. eCollection 2014.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [11] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [12] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [13] 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.
• [14] 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.
• [15] Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion. J Biomed Res. 2020 Jun 30;34(5):369-378. doi: 10.7555/JBR.34.20200013.
• [16] 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.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.