Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7V5DAR)

• DOT Name: Sex comb on midleg-like protein 1 (SCML1)
• Gene Name: SCML1
• Related Disease:
  Lung cancer
  Lung carcinoma
• UniProt ID: SCML1_HUMAN
• Pfam ID: PF00536
• Sequence:
  MMSNSSSEIDVIKTRIPTYDEDDNTILYAYETKPEFVNKEPNIVSDASCNTEEQLKTVDD
  VLIHCQVIYDALQNLDKKIDVIRRKVSKIQRFHARSLWTNHKRYGYKKHSYRLVKKLKLQ
  KMKKNEVYETFSYPESYSPTLPVSRRENNSPSNLPRPSFCMEEYQRAELEEDPILSRTPS
  PVHPSDFSEHNCQPYYASDGATYGSSSGLCLGNPRADSIHNTYSTDHASAAPPSVTRSPV
  ENDGYIEEGSITKHPSTWSVEAVVLFLKQTDPLALCPLVDLFRSHEIDGKALLLLTSDVL
  LKHLGVKLGTAVKLCYYIDRLKQGKCFEN
• Function: Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. May be involved in spermatogenesis during sexual maturation.
• Tissue Specificity: Ubiquitous. Expressed in fetal and adult tissues.
• KEGG Pathway: Polycomb repressive complex (hsa03083)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]

2 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 Sex comb on midleg-like protein 1 (SCML1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sex comb on midleg-like protein 1 (SCML1).	[12]

15 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 Sex comb on midleg-like protein 1 (SCML1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sex comb on midleg-like protein 1 (SCML1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sex comb on midleg-like protein 1 (SCML1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Sex comb on midleg-like protein 1 (SCML1).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Sex comb on midleg-like protein 1 (SCML1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Sex comb on midleg-like protein 1 (SCML1).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sex comb on midleg-like protein 1 (SCML1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Sex comb on midleg-like protein 1 (SCML1).	[15]

References

• [1] Circular RNA circNOL10 Inhibits Lung Cancer Development by Promoting SCLM1-Mediated Transcriptional Regulation of the Humanin Polypeptide Family.Adv Sci (Weinh). 2018 Nov 16;6(2):1800654. doi: 10.1002/advs.201800654. eCollection 2019 Jan 23.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] 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.
• [10] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [11] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.