Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTG7G3P)

• DOT Name: Modulator of smoothened protein (MOSMO)
• Synonyms: Attenuator of hedgehog
• Gene Name: MOSMO
• UniProt ID: MOSMO_HUMAN
• Pfam ID: PF18800
• Sequence:
  MDKLTIISGCLFLAADIFAIASIANPDWINTGESAGALTVGLVRQCQTIHGRDRTCIPPR
  LPPEWVTTLFFIIMGIISLTVTCGLLVASHWRREATKYARWIAFTGMILFCMAALIFPIG
  FYINEVGGQPYKLPNNTVVGSSYVLFVLSIFFTIVGLLFAGKVCLPG
• Function: Acts as a negative regulator of hedgehog signaling probably by promoting internalization and subsequent degradation of smoothened protein (SMO) present in the ciliary membrane. Plays a role in sonic hedgehog (SHH)-induced spinal neural progenitor cells differentiation.
• KEGG Pathway: Hedgehog sig.ling pathway (hsa04340)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Modulator of smoothened protein (MOSMO).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Modulator of smoothened protein (MOSMO).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Modulator of smoothened protein (MOSMO).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Modulator of smoothened protein (MOSMO).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Modulator of smoothened protein (MOSMO).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Modulator of smoothened protein (MOSMO).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Modulator of smoothened protein (MOSMO).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Modulator of smoothened protein (MOSMO).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Modulator of smoothened protein (MOSMO).	[10]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Modulator of smoothened protein (MOSMO).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Modulator of smoothened protein (MOSMO).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Modulator of smoothened protein (MOSMO).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Modulator of smoothened protein (MOSMO).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] 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.
• [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] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [11] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.