Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2FDMA1)

• DOT Name: Soluble lamin-associated protein of 75 kDa (FAM169A)
• Synonyms: SLAP75; Protein FAM169A
• Gene Name: FAM169A
• UniProt ID: F169A_HUMAN
• Sequence:
  MAFPVDMLENCSHEELENSAEDYMSDLRCGDPENPECFSLLNITIPISLSNVGFVPLYGG
  DQTQKILALFAPEDSLTAVALYLADQWWAIDDIVKTSVPSREGLKQVSTLGERVVLYVLN
  RIIYRKQEMERNEIPFLCHSSTDYAKILWKKGEAIGFYSVKPTGSICASFLTQSYQLPVL
  DTMFLRKKYRGKDFGLHMLEDFVDSFTEDALGLRYPLSSLMYTACKQYFEKYPGDHELLW
  EVEGVGHWYQRIPVTRALQREALKILALSQNEPKRPMSGEYGPASVPEYEARTEDNQSSE
  MQLTIDSLKDAFASTSEGHDKTSVSTHTRSGNLKRPKIGKRFQDSEFSSSQGEDEKTSQT
  SLTASINKLESTARPSESSEEFLEEEPEQRGIEFEDESSDRDARPALETQPQQEKQDGEK
  ESELEPMNGEIMDDSLKTSLITEEEDSTSEVLDEELKLQPFNSSEDSTNLVPLVVESSKP
  PEVDAPDKTPRIPDSEMLMDEGTSDEKGHMEEKLSLLPRKKAHLGSSDNVATMSNEERSD
  GGFPNSVIAEFSEEPVSENLSPNTTSSLEDQGEEGVSEPQETSTALPQSSLIEVELEDVP
  FSQNAGQKNQSEEQSEASSEQLDQFTQSAEKAVDSSSEEIEVEVPVVDRRNLRRKAKGHK
  GPAKKKAKLT
• Reactome Pathway: RHOF GTPase cycle (R-HSA-9035034)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Soluble lamin-associated protein of 75 kDa (FAM169A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[7]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Soluble lamin-associated protein of 75 kDa (FAM169A).	[14]

3 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 Soluble lamin-associated protein of 75 kDa (FAM169A).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Soluble lamin-associated protein of 75 kDa (FAM169A).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Soluble lamin-associated protein of 75 kDa (FAM169A).	[13]

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 phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [3] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [8] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.