Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE4IU5U)

• DOT Name: Calpain-9 (CAPN9)
• Synonyms: EC 3.4.22.-; Digestive tract-specific calpain; New calpain 4; nCL-4; Protein CG36
• Gene Name: CAPN9
• Related Disease:
  Nephropathy
  Pulmonary fibrosis
  Non-insulin dependent diabetes
• UniProt ID: CAN9_HUMAN
• PDB ID: 1ZIV; 2P0R
• EC Number: 3.4.22.-
• Pfam ID: PF01067 ; PF13833 ; PF00648
• Sequence:
  MPYLYRAPGPQAHPVPKDARITHSSGQSFEQMRQECLQRGTLFEDADFPASNSSLFYSER
  PQIPFVWKRPGEIVKNPEFILGGATRTDICQGELGDCWLLAAIASLTLNQKALARVIPQD
  QSFGPGYAGIFHFQFWQHSEWLDVVIDDRLPTFRDRLVFLHSADHNEFWSALLEKAYAKL
  NGSYEALKGGSAIEAMEDFTGGVAETFQTKEAPENFYEILEKALKRGSLLGCFIDTRSAA
  ESEARTPFGLIKGHAYSVTGIDQVSFRGQRIELIRIRNPWGQVEWNGSWSDSSPEWRSVG
  PAEQKRLCHTALDDGEFWMAFKDFKAHFDKVEICNLTPDALEEDAIHKWEVTVHQGSWVR
  GSTAGGCRNFLDTFWTNPQIKLSLTEKDEGQEECSFLVALMQKDRRKLKRFGANVLTIGY
  AIYECPDKDEHLNKDFFRYHASRARSKTFINLREVSDRFKLPPGEYILIPSTFEPHQEAD
  FCLRIFSEKKAITRDMDGNVDIDLPEPPKPTPPDQETEEEQRFRALFEQVAGEDMEVTAE
  ELEYVLNAVLQKKKDIKFKKLSLISCKNIISLMDTSGNGKLEFDEFKVFWDKLKQWINLF
  LRFDADKSGTMSTYELRTALKAAGFQLSSHLLQLIVLRYADEELQLDFDDFLNCLVRLEN
  ASRVFQALSTKNKEFIHLNINEFIHLTMNI
• Function: Calcium-regulated non-lysosomal thiol-protease.
• Tissue Specificity: Expressed predominantly in stomach.
• Reactome Pathway: Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephropathy	DISXWP4P	Strong	Biomarker	[1]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Calpain-9 (CAPN9).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Calpain-9 (CAPN9).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Calpain-9 (CAPN9).	[6]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Calpain-9 (CAPN9).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Calpain-9 (CAPN9).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Calpain-9 (CAPN9).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Calpain-9 (CAPN9).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Calpain-9 (CAPN9).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Calpain-9 (CAPN9).	[6]

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 Calpain-9 (CAPN9).	[10]

References

• [1] Expression and effect of Calpain9 gene genetic polymorphism on slaughter indicators and intramuscular fat content in chickens.Poult Sci. 2018 Oct 1;97(10):3414-3420. doi: 10.3382/ps/pey232.
• [2] Calpain 9 as a therapeutic target in TGF-induced mesenchymal transition and fibrosis.Sci Transl Med. 2019 Jul 17;11(501):eaau2814. doi: 10.1126/scitranslmed.aau2814.
• [3] The calpain family and human disease.Trends Mol Med. 2001 Aug;7(8):355-62. doi: 10.1016/s1471-4914(01)02049-4.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [7] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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.