Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOQIVV0)

• DOT Name: Late cornified envelope-like proline-rich protein 1 (LELP1)
• Synonyms: Novel small proline-rich protein
• Gene Name: LELP1
• Related Disease:
  Asthma
  Atopic dermatitis
• UniProt ID: LELP1_HUMAN
• Pfam ID: PF15042
• Sequence:
  MSSDDKSKSNDPKTEPKNCDPKCEQKCESKCQPSCLKKLLQRCFEKCPWEKCPAPPKCLP
  CPSQSPSSCPPQPCTKPCPPKCPSSCPHACPPPCPPPE
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Limited	Genetic Variation	[1]
Atopic dermatitis	DISTCP41	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Late cornified envelope-like proline-rich protein 1 (LELP1).	[3]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Late cornified envelope-like proline-rich protein 1 (LELP1).	[4]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Late cornified envelope-like proline-rich protein 1 (LELP1).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Late cornified envelope-like proline-rich protein 1 (LELP1).	[6]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Late cornified envelope-like proline-rich protein 1 (LELP1).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Late cornified envelope-like proline-rich protein 1 (LELP1).	[8]

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 Late cornified envelope-like proline-rich protein 1 (LELP1).	[7]

References

• [1] Association of a Single Nucleotide Polymorphism in a Late Cornified Envelope-like Proline-rich 1 Gene (LELP1) with Atopic Dermatitis.Acta Derm Venereol. 2016 May;96(4):459-63. doi: 10.2340/00015555-2301.
• [2] Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype.Acta Derm Venereol. 2017 Jan 4;97(1):36-41. doi: 10.2340/00015555-2482.
• [3] 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.
• [4] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [6] 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.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.