Details of Drug Off-Target (DOT)

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

• DOT Name: Methionine-R-sulfoxide reductase B1 (MSRB1)
• Synonyms: MsrB1; EC 1.8.4.12; EC 1.8.4.14; Selenoprotein X; SelX
• Gene Name: MSRB1
• UniProt ID: MSRB1_HUMAN
• PDB ID: 3MAO
• EC Number: 1.8.4.12; 1.8.4.14
• Pfam ID: PF01641
• Sequence:
  MSFCSFFGGEVFQNHFEPGVYVCAKCGYELFSSRSKYAHSSPWPAFTETIHADSVAKRPE
  HNRSEALKVSCGKCGNGLGHEFLNDGPKPGQSRFUIFSSSLKFVPKGKETSASQGH
• Function: Methionine-sulfoxide reductase that specifically reduces methionine (R)-sulfoxide back to methionine. While in many cases, methionine oxidation is the result of random oxidation following oxidative stress, methionine oxidation is also a post-translational modification that takes place on specific residue. Acts as a regulator of actin assembly by reducing methionine (R)-sulfoxide mediated by MICALs (MICAL1, MICAL2 or MICAL3) on actin, thereby promoting filament repolymerization. Plays a role in innate immunity by reducing oxidized actin, leading to actin repolymerization in macrophages.
• Reactome Pathway: Protein repair (R-HSA-5676934)

Molecular Interaction Atlas (MIA) of This DOT

1 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 Methionine-R-sulfoxide reductase B1 (MSRB1).	[1]

11 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 Methionine-R-sulfoxide reductase B1 (MSRB1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Methionine-R-sulfoxide reductase B1 (MSRB1).	[12]

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] 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.
• [4] 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.
• [5] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [6] 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.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.