Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH0PF56)

• DOT Name: StAR-related lipid transfer protein 5 (STARD5)
• Synonyms: START domain-containing protein 5; StARD5
• Gene Name: STARD5
• UniProt ID: STAR5_HUMAN
• PDB ID: 2R55
• Pfam ID: PF01852
• Sequence:
  MDPALAAQMSEAVAEKMLQYRRDTAGWKICREGNGVSVSWRPSVEFPGNLYRGEGIVYGT
  LEEVWDCVKPAVGGLRVKWDENVTGFEIIQSITDTLCVSRTSTPSAAMKLISPRDFVDLV
  LVKRYEDGTISSNATHVEHPLCPPKPGFVRGFNHPCGCFCEPLPGEPTKTNLVTFFHTDL
  SGYLPQNVVDSFFPRSMTRFYANLQKAVKQFHE
• Function: May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols.
• Reactome Pathway: Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DOT

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 StAR-related lipid transfer protein 5 (STARD5).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of StAR-related lipid transfer protein 5 (STARD5).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of StAR-related lipid transfer protein 5 (STARD5).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of StAR-related lipid transfer protein 5 (STARD5).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of StAR-related lipid transfer protein 5 (STARD5).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of StAR-related lipid transfer protein 5 (STARD5).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of StAR-related lipid transfer protein 5 (STARD5).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of StAR-related lipid transfer protein 5 (STARD5).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of StAR-related lipid transfer protein 5 (STARD5).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of StAR-related lipid transfer protein 5 (STARD5).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of StAR-related lipid transfer protein 5 (STARD5).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of StAR-related lipid transfer protein 5 (STARD5).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of StAR-related lipid transfer protein 5 (STARD5).	[14]

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 decreases the methylation of StAR-related lipid transfer protein 5 (STARD5).	[10]

References

• [1] 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.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [12] 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.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.