Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXRU9XQ)

• DOT Name: Lipid droplet-associated hydrolase (LDAH)
• Synonyms: EC 3.1.1.-; Lipid droplet-associated serine hydrolase; hLDAH
• Gene Name: LDAH
• Related Disease:
  Crohn disease
  Prostate carcinoma
  Sensorineural hearing loss disorder
  Ulcerative colitis
  Prostate cancer
  Prostate neoplasm
• UniProt ID: LDAH_HUMAN
• EC Number: 3.1.1.-
• Pfam ID: PF10230
• Sequence:
  MDSELKEEIPVHEEFILCGGAETQVLKCGPWTDLFHDQSVKRPKLLIFIIPGNPGFSAFY
  VPFAKALYSLTNRRFPVWTISHAGHALAPKDKKILTTSEDSNAQEIKDIYGLNGQIEHKL
  AFLRTHVPKDMKLVLIGHSIGSYFTLQMLKRVPELPVIRAFLLFPTIERMSESPNGRIAT
  PLLCWFRYVLYVTGYLLLKPCPETIKSLLIRRGLQVMNLENEFSPLNILEPFCLANAAYL
  GGQEMMEVVKRDDETIKEHLCKLTFYYGTIDPWCPKEYYEDIKKDFPEGDIRLCEKNIPH
  AFITHFNQEMADMIADSLKDDLSKM
• Function: Probable serine lipid hydrolase associated with lipid droplets. Appears to lack cholesterol esterase activity. Appears to lack triglyceride lipase activity. Highly expressed in macrophage-rich areas in atherosclerotic lesions, suggesting that it could promote cholesterol ester turnover in macrophages.
• Tissue Specificity: Present in macrophage-rich areas in atherosclerotic lesionsv(at protein level).

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[2]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Limited	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Lipid droplet-associated hydrolase (LDAH).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lipid droplet-associated hydrolase (LDAH).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lipid droplet-associated hydrolase (LDAH).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Lipid droplet-associated hydrolase (LDAH).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Lipid droplet-associated hydrolase (LDAH).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Lipid droplet-associated hydrolase (LDAH).	[9]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Lipid droplet-associated hydrolase (LDAH).	[12]

2 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 affects the methylation of Lipid droplet-associated hydrolase (LDAH).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lipid droplet-associated hydrolase (LDAH).	[11]

References

• [1] Characterization of genetic loci that affect susceptibility to inflammatory bowel diseases in African Americans.Gastroenterology. 2015 Nov;149(6):1575-1586. doi: 10.1053/j.gastro.2015.07.065. Epub 2015 Aug 14.
• [2] Loss of LDAH associated with prostate cancer and hearing loss.Hum Mol Genet. 2018 Dec 15;27(24):4194-4203. doi: 10.1093/hmg/ddy310.
• [3] Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population.Nat Genet. 2010 Sep;42(9):751-4. doi: 10.1038/ng.635. Epub 2010 Aug 1.
• [4] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [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] 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.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.