Details of Drug Off-Target (DOT)

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

• DOT Name: Small integral membrane protein 11 (SMIM11)
• Gene Name: SMIM11
• UniProt ID: SIM11_HUMAN
• Pfam ID: PF14981
• Sequence: MNWKVLEHVPLLLYILAAKTLILCLTFAGVKMYQRKRLEAKQQKLEAERKKQSEKKDN
• Tissue Specificity: Expressed in heart, spleen, liver, stomach, muscle, lung, testis, skin, PBL and bone marrow.

Molecular Interaction Atlas (MIA) of This DOT

9 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 Small integral membrane protein 11 (SMIM11).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Small integral membrane protein 11 (SMIM11).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Small integral membrane protein 11 (SMIM11).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small integral membrane protein 11 (SMIM11).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Small integral membrane protein 11 (SMIM11).	[5]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Small integral membrane protein 11 (SMIM11).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Small integral membrane protein 11 (SMIM11).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Small integral membrane protein 11 (SMIM11).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Small integral membrane protein 11 (SMIM11).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Small integral membrane protein 11 (SMIM11).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Global gene expression analysis reveals novel transcription factors associated with long-term low-level exposure of EA.hy926 human endothelial cells to bisphenol A. Chem Biol Interact. 2023 Aug 25;381:110571. doi: 10.1016/j.cbi.2023.110571. Epub 2023 May 25.