Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD2DN1Z)

• DOT Name: Caspase activity and apoptosis inhibitor 1 (CAAP1)
• Synonyms: Conserved anti-apoptotic protein; CAAP
• Gene Name: CAAP1
• Related Disease: Arrhythmia
• UniProt ID: CAAP1_HUMAN
• Pfam ID: PF15335
• Sequence:
  MTGKKSSREKRRKRSSQEAAAALAAPDIVPALASGSSGSTSGCGSAGGCGSVSCCGNANF
  SGSVTGGGSGGSCWGGSSVERSERRKRRSTDSSSVSGSLQQETKYILPTLEKELFLAEHS
  DLEEGGLDLTVSLKPVSFYISDKKEMLQQCFCIIGEKKLQKMLPDVLKNCSIEEIKKLCQ
  EQLELLSEKKILKILEGDNGMDSDMEEEADDGSKMGSDLVSQQDICIDSASSVRENKQPE
  GLELKQGKGEDSDVLSINADAYDSDIEGPCNEEAAAPEAPENTVQSEAGQIDDLEKDIEK
  SVNEILGLAESSPNEPKAATLAVPPPEDVQPSAQQLELLELEMRARAIKALMKAGDIKKP
  A
• Function: Anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arrhythmia	DISFF2NI	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Caspase activity and apoptosis inhibitor 1 (CAAP1).	[5]

References

• [1] Predictors of arrhythmia recurrence after balloon cryoablation of atrial fibrillation: the value of CAAP-AF risk scoring system.J Interv Card Electrophysiol. 2017 Aug;49(2):129-135. doi: 10.1007/s10840-017-0248-4. Epub 2017 Apr 18.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] 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.
• [7] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.