Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7C8GFN)

• DOT Name: cAMP-dependent protein kinase inhibitor beta (PKIB)
• Synonyms: PKI-beta
• Gene Name: PKIB
• Related Disease:
  Breast cancer
  Breast carcinoma
  Hepatitis C virus infection
  Huntington disease
  Prostate cancer
  Prostate carcinoma
• UniProt ID: IPKB_HUMAN
• Pfam ID: PF02827
• Sequence:
  MRTDSSKMTDVESGVANFASSARAGRRNALPDIQSSAATDGTSDLPLKLEALSVKEDAKE
  KDEKTTQDQLEKPQNEEK
• Function: Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[2]
Huntington disease	DISQPLA4	Strong	Biomarker	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of cAMP-dependent protein kinase inhibitor beta (PKIB).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of cAMP-dependent protein kinase inhibitor beta (PKIB).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of cAMP-dependent protein kinase inhibitor beta (PKIB).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[15]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[16]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[22]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[23]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[24]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of cAMP-dependent protein kinase inhibitor beta (PKIB).	[25]

References

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• [2] Impact of IFNL4 Genetic Variants on Sustained Virologic Response and Viremia in Hepatitis C Virus Genotype 3 Patients.J Interferon Cytokine Res. 2019 Oct;39(10):642-649. doi: 10.1089/jir.2019.0013. Epub 2019 Jul 1.
• [3] Early transcriptional changes linked to naturally occurring Huntington's disease mutations in neural derivatives of human embryonic stem cells.Hum Mol Genet. 2012 Sep 1;21(17):3883-95. doi: 10.1093/hmg/dds216. Epub 2012 Jun 7.
• [4] Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways.Oncogene. 2009 Aug 13;28(32):2849-59. doi: 10.1038/onc.2009.144. Epub 2009 Jun 1.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [8] 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.
• [9] 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.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] 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.
• [12] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [13] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [14] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [19] 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.
• [20] 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.
• [21] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [22] 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.
• [23] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [24] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [25] Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.