Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBKC6PT)

• DOT Name: Fat storage-inducing transmembrane protein 1 (FITM1)
• Synonyms: Fat-inducing protein 1
• Gene Name: FITM1
• Related Disease:
  Diabetic kidney disease
  Colorectal carcinoma
  Neoplasm
• UniProt ID: FITM1_HUMAN
• Sequence:
  MERGPVVGAGLGAGARIQALLGCLLKVLLWVASALLYFGSEQAARLLGSPCLRRLYHAWL
  AAVVIFGPLLQFHVNPRTIFASHGNFFNIKFVNSAWGWTCTFLGGFVLLVVFLATRRVAV
  TARHLSRLVVGAAVWRGAGRAFLLIEDLTGSCFEPLPQGLLLHELPDRRSCLAAGHQWRG
  YTVSSHTFLLTFCCLLMAEEAAVFAKYLAHGLPAGAPLRLVFLLNVLLLGLWNFLLLCTV
  IYFHQYTHKVVGAAVGTFAWYLTYGSWYHQPWSPGSPGHGLFPRPHSSRKHN
• Function: Plays an important role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis. Directly binds to diacylglycerol (DAGs) and triacylglycerol.
• Tissue Specificity: Primarily expressed in heart and skeletal muscle.
• Reactome Pathway: Lipid particle organization (R-HSA-8964572)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Fat storage-inducing transmembrane protein 1 (FITM1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fat storage-inducing transmembrane protein 1 (FITM1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fat storage-inducing transmembrane protein 1 (FITM1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Fat storage-inducing transmembrane protein 1 (FITM1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Fat storage-inducing transmembrane protein 1 (FITM1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fat storage-inducing transmembrane protein 1 (FITM1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fat storage-inducing transmembrane protein 1 (FITM1).	[10]

References

• [1] Vascular endothelial growth factor (VEGF) and VEGF receptors in diabetic nephropathy: expression studies in biopsies of type 2 diabetic patients.Ren Fail. 2001 May-Jul;23(3-4):483-93. doi: 10.1081/jdi-100104731.
• [2] Multiple rounds of one sample versus two sample faecal immunochemical test-based colorectal cancer screening: a population-based study.Lancet Gastroenterol Hepatol. 2019 Aug;4(8):622-631. doi: 10.1016/S2468-1253(19)30176-1. Epub 2019 Jun 10.
• [3] Expression and functional significance of vascular endothelial growth factor receptors in human tumor cells.Lab Invest. 1999 Dec;79(12):1573-82.
• [4] 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.
• [5] 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.
• [6] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [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.