Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC1WFNO)

• DOT Name: Adenylyl cyclase-associated protein 2 (CAP2)
• Synonyms: CAP 2
• Gene Name: CAP2
• Related Disease:
  Atrial fibrillation
  Bipolar disorder
  Bronchopulmonary dysplasia
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Familial dilated cardiomyopathy
  Neoplasm
  Stroke
  Obsolete familial isolated dilated cardiomyopathy
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Gastric cancer
  Melanoma
  Metastatic malignant neoplasm
  Myopathy
  Stomach cancer
• UniProt ID: CAP2_HUMAN
• Pfam ID: PF08603 ; PF01213
• Sequence:
  MANMQGLVERLERAVSRLESLSAESHRPPGNCGEVNGVIAGVAPSVEAFDKLMDSMVAEF
  LKNSRILAGDVETHAEMVHSAFQAQRAFLLMASQYQQPHENDVAALLKPISEKIQEIQTF
  RERNRGSNMFNHLSAVSESIPALGWIAVSPKPGPYVKEMNDAATFYTNRVLKDYKHSDLR
  HVDWVKSYLNIWSELQAYIKEHHTTGLTWSKTGPVASTVSAFSVLSSGPGLPPPPPPLPP
  PGPPPLFENEGKKEESSPSRSALFAQLNQGEAITKGLRHVTDDQKTYKNPSLRAQGGQTQ
  SPTKSHTPSPTSPKSYPSQKHAPVLELEGKKWRVEYQEDRNDLVISETELKQVAYIFKCE
  KSTIQIKGKVNSIIIDNCKKLGLVFDNVVGIVEVINSQDIQIQVMGRVPTISINKTEGCH
  IYLSEDALDCEIVSAKSSEMNILIPQDGDYREFPIPEQFKTAWDGSKLITEPAEIMA
• Function: May have a regulatory bifunctional role.
• Reactome Pathway: Role of ABL in ROBO-SLIT signaling (R-HSA-428890)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[2]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[2]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[3]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[3]
Familial dilated cardiomyopathy	DISBHDU9	Strong	GermlineCausalMutation	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Stroke	DISX6UHX	Strong	Genetic Variation	[6]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[5]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[5]
Melanoma	DIS1RRCY	Limited	Altered Expression	[5]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[5]
Myopathy	DISOWG27	Limited	Biomarker	[7]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Adenylyl cyclase-associated protein 2 (CAP2) affects the response to substance of Fluorouracil.	[33]

24 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 Adenylyl cyclase-associated protein 2 (CAP2).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[18]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[19]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[21]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[28]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[30]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[31]
Taurine	DMVW7N3	Investigative	Taurine decreases the expression of Adenylyl cyclase-associated protein 2 (CAP2).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Adenylyl cyclase-associated protein 2 (CAP2).	[29]

References

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• [2] A linkage and exome study implicates rare variants of KANK4 and CAP2 in bipolar disorder in a multiplex family.Bipolar Disord. 2020 Feb;22(1):70-78. doi: 10.1111/bdi.12815. Epub 2019 Aug 21.
• [3] Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays disease onset.JCI Insight. 2019 Mar 21;4(6):e124629. doi: 10.1172/jci.insight.124629. eCollection 2019 Mar 21.
• [4] CAP2 mutation leads to impaired actin dynamics and associates with supraventricular tachycardia and dilated cardiomyopathy. J Med Genet. 2019 Apr;56(4):228-235. doi: 10.1136/jmedgenet-2018-105498. Epub 2018 Dec 5.
• [5] CAP2 is a Valuable Biomarker for Diagnosis and Prognostic in Patients with Gastric Cancer.Pathol Oncol Res. 2020 Jan;26(1):273-279. doi: 10.1007/s12253-018-0450-4. Epub 2018 Jul 26.
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• [7] CAP2 deficiency delays myofibril actin cytoskeleton differentiation and disturbs skeletal muscle architecture and function.Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8397-8402. doi: 10.1073/pnas.1813351116. Epub 2019 Apr 8.
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• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
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• [16] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
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• [18] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [19] 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.
• [20] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [23] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [24] Effects of resveratrol on gene expression in renal cell carcinoma. Cancer Biol Ther. 2004 Sep;3(9):882-8. doi: 10.4161/cbt.3.9.1056. Epub 2004 Sep 21.
• [25] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [26] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [27] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [29] 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.
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• [31] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.
• [32] Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.
• [33] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.