Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNM186C)

• DOT Name: Fatty acid-binding protein 5 (FABP5)
• Synonyms: Epidermal-type fatty acid-binding protein; E-FABP; Fatty acid-binding protein, epidermal; Psoriasis-associated fatty acid-binding protein homolog; PA-FABP
• Gene Name: FABP5
• UniProt ID: FABP5_HUMAN
• PDB ID: 1B56; 1JJJ; 4AZM; 4AZR; 4LKP; 4LKT; 5HZ5; 5UR9; 7FWI; 7FXD; 7FY0; 7FYD; 7G01; 7G04; 7G0B; 7G0E; 7G1Q
• Pfam ID: PF00061
• Sequence:
  MATVQQLEGRWRLVDSKGFDEYMKELGVGIALRKMGAMAKPDCIITCDGKNLTIKTESTL
  KTTQFSCTLGEKFEETTADGRKTQTVCNFTDGALVQHQEWDGKESTITRKLKDGKLVVEC
  VMNNVTCTRIYEKVE
• Function: Intracellular carrier for long-chain fatty acids and related active lipids, such as endocannabinoids, that regulate the metabolism and actions of the ligands they bind. In addition to the cytosolic transport, selectively delivers specific fatty acids from the cytosol to the nucleus, wherein they activate nuclear receptors. Delivers retinoic acid to the nuclear receptor peroxisome proliferator-activated receptor delta; which promotes proliferation and survival. May also serve as a synaptic carrier of endocannabinoid at central synapses and thus controls retrograde endocannabinoid signaling. Modulates inflammation by regulating PTGES induction via NF-kappa-B activation, and prostaglandin E2 (PGE2) biosynthesis during inflammation. May be involved in keratinocyte differentiation.
• Tissue Specificity: Keratinocytes; highly expressed in psoriatic skin . Expressed in brain gray matter .
• KEGG Pathway: PPAR sig.ling pathway (hsa03320)
• Reactome Pathway:
  Signaling by Retinoic Acid (R-HSA-5362517)
  Neutrophil degranulation (R-HSA-6798695)
  Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DOT

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Fatty acid-binding protein 5 (FABP5).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fatty acid-binding protein 5 (FABP5).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fatty acid-binding protein 5 (FABP5).	[18]

21 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 Fatty acid-binding protein 5 (FABP5).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fatty acid-binding protein 5 (FABP5).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Fatty acid-binding protein 5 (FABP5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fatty acid-binding protein 5 (FABP5).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fatty acid-binding protein 5 (FABP5).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fatty acid-binding protein 5 (FABP5).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Fatty acid-binding protein 5 (FABP5).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Fatty acid-binding protein 5 (FABP5).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Fatty acid-binding protein 5 (FABP5).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Fatty acid-binding protein 5 (FABP5).	[2]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Fatty acid-binding protein 5 (FABP5).	[11]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Fatty acid-binding protein 5 (FABP5).	[12]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Fatty acid-binding protein 5 (FABP5).	[13]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Fatty acid-binding protein 5 (FABP5).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fatty acid-binding protein 5 (FABP5).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fatty acid-binding protein 5 (FABP5).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fatty acid-binding protein 5 (FABP5).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fatty acid-binding protein 5 (FABP5).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Fatty acid-binding protein 5 (FABP5).	[20]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Fatty acid-binding protein 5 (FABP5).	[21]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Fatty acid-binding protein 5 (FABP5).	[2]

References

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• [2] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [3] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [12] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [13] Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun. 2008 Aug 8;372(4):785-91.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.