Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA425AX)

• DOT Name: Serine protease 1 (PRSS1)
• Synonyms: EC 3.4.21.4; Anionic trypsin I; Anionic trypsin-I; Beta-trypsin; Cationic trypsinogen; Pretrypsinogen I; Trypsin I; Trypsin-1
• Gene Name: PRSS1
• Related Disease:
  Hereditary chronic pancreatitis
  Malignant pancreatic neoplasm
• UniProt ID: TRY1_HUMAN
• PDB ID: 1FXY; 1TRN; 2RA3; 4WWY; 4WXV; 7QE8; 7QE9; 8H3S
• EC Number: 3.4.21.4
• Pfam ID: PF00089
• Sequence:
  MNPLLILTFVAAALAAPFDDDDKIVGGYNCEENSVPYQVSLNSGYHFCGGSLINEQWVVS
  AGHCYKSRIQVRLGEHNIEVLEGNEQFINAAKIIRHPQYDRKTLNNDIMLIKLSSRAVIN
  ARVSTISLPTAPPATGTKCLISGWGNTASSGADYPDELQCLDAPVLSQAKCEASYPGKIT
  SNMFCVGFLEGGKDSCQGDSGGPVVCNGQLQGVVSWGDGCAQKNKPGVYTKVYNYVKWIK
  NTIAANS
• Function: Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Pancreatic secretion (hsa04972)
  Protein digestion and absorption (hsa04974)
  Influenza A (hsa05164)
• Reactome Pathway:
  Uptake of dietary cobalamins into enterocytes (R-HSA-9758881)
  Activation of Matrix Metalloproteinases (R-HSA-1592389)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary chronic pancreatitis	DISF0J1Q	Definitive	Autosomal dominant	[1]
Malignant pancreatic neoplasm	DISH4FJX	Moderate	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Serine protease 1 (PRSS1) increases the Alcoholic pancreatitis ADR of Ethanol.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Serine protease 1 (PRSS1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine protease 1 (PRSS1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine protease 1 (PRSS1).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Serine protease 1 (PRSS1).	[6]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Serine protease 1 (PRSS1).	[7]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Serine protease 1 (PRSS1).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Serine protease 1 (PRSS1).	[9]

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 affects the methylation of Serine protease 1 (PRSS1).	[10]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Current Approaches to Pancreatic Cancer Screening. Am J Pathol. 2019 Jan;189(1):22-35. doi: 10.1016/j.ajpath.2018.09.013.
• [3] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [4] 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.
• [5] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [8] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [9] 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.
• [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] Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis. Nat Genet. 2012 Dec;44(12):1349-54. doi: 10.1038/ng.2466. Epub 2012 Nov 11.