Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8IEN62)

• DOT Name: Solute carrier family 66 member 3 (SLC66A3)
• Synonyms: PQ-loop repeat-containing protein 3
• Gene Name: SLC66A3
• Related Disease:
  Liver cancer
  Uterine fibroids
• UniProt ID: S66A3_HUMAN
• Pfam ID: PF04193
• Sequence:
  MEAALLGLCNWSTLGVCAALKLPQISAVLAARSARGLSLPSLLLELAGFLVFLRYQCYYG
  YPPLTYLEYPILIAQDVILLLCIFHFNGNVKQATPYIAVLVSSWFILALQKWIIDLAMNL
  CTFISAASKFAQLQCLWKTRDSGTVSALTWSLSSYTCATRIITTLMTTNDFTILLRFVIM
  LALNIWVTVTVLRYRKTAIKAE

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[2]

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 Solute carrier family 66 member 3 (SLC66A3).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Solute carrier family 66 member 3 (SLC66A3).	[16]

13 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 Solute carrier family 66 member 3 (SLC66A3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Solute carrier family 66 member 3 (SLC66A3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Solute carrier family 66 member 3 (SLC66A3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Solute carrier family 66 member 3 (SLC66A3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Solute carrier family 66 member 3 (SLC66A3).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Solute carrier family 66 member 3 (SLC66A3).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Solute carrier family 66 member 3 (SLC66A3).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Solute carrier family 66 member 3 (SLC66A3).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Solute carrier family 66 member 3 (SLC66A3).	[12]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Solute carrier family 66 member 3 (SLC66A3).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Solute carrier family 66 member 3 (SLC66A3).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Solute carrier family 66 member 3 (SLC66A3).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Solute carrier family 66 member 3 (SLC66A3).	[15]

References

• [1] Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.PLoS One. 2014 Jul 24;9(7):e102579. doi: 10.1371/journal.pone.0102579. eCollection 2014.
• [2] Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.Nat Commun. 2019 Oct 24;10(1):4857. doi: 10.1038/s41467-019-12536-4.
• [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] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
• [13] 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.
• [14] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [15] 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.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.