Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFFF738)

• DOT Name: Chymotrypsinogen B (CTRB1)
• Synonyms: EC 3.4.21.1
• Gene Name: CTRB1
• Related Disease:
  Age-related macular degeneration
  Coronary atherosclerosis
  Coronary heart disease
  Non-insulin dependent diabetes
  Chronic pancreatitis
  Neoplasm
  Pancreatitis
• UniProt ID: CTRB1_HUMAN
• EC Number: 3.4.21.1
• Pfam ID: PF00089
• Sequence:
  MASLWLLSCFSLVGAAFGCGVPAIHPVLSGLSRIVNGEDAVPGSWPWQVSLQDKTGFHFC
  GGSLISEDWVVTAAHCGVRTSDVVVAGEFDQGSDEENIQVLKIAKVFKNPKFSILTVNND
  ITLLKLATPARFSQTVSAVCLPSADDDFPAGTLCATTGWGKTKYNANKTPDKLQQAALPL
  LSNAECKKSWGRRITDVMICAGASGVSSCMGDSGGPLVCQKDGAWTLVGIVSWGSDTCST
  SSPGVYARVTKLIPWVQKILAAN
• KEGG Pathway:
  Pancreatic secretion (hsa04972)
  Protein digestion and absorption (hsa04974)
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[1]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[3]
Chronic pancreatitis	DISBUOMJ	Limited	Genetic Variation	[4]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[5]
Pancreatitis	DIS0IJEF	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Chymotrypsinogen B (CTRB1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Chymotrypsinogen B (CTRB1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Chymotrypsinogen B (CTRB1).	[8]

References

• [1] Genome-wide analysis of disease progression in age-related macular degeneration.Hum Mol Genet. 2018 Mar 1;27(5):929-940. doi: 10.1093/hmg/ddy002.
• [2] Genetic overlap between birthweight and adult cardiometabolic diseases has implications for genomic medicine.Sci Rep. 2019 Mar 11;9(1):4076. doi: 10.1038/s41598-019-40834-w.
• [3] Functional and association analysis of an Amerindian-derived population-specific p.(Thr280Met) variant in RBPJL, a component of the PTF1 complex.Eur J Hum Genet. 2018 Feb;26(2):238-246. doi: 10.1038/s41431-017-0062-6. Epub 2018 Jan 4.
• [4] Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis.Gut. 2018 Oct;67(10):1855-1863. doi: 10.1136/gutjnl-2017-314454. Epub 2017 Jul 28.
• [5] Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma.Proc Natl Acad Sci U S A. 1990 Sep;87(17):6791-4. doi: 10.1073/pnas.87.17.6791.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [8] 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.