Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0IRJBY)

• DOT Name: BMP-2-inducible protein kinase (BMP2K)
• Synonyms: BIKe; EC 2.7.11.1
• Gene Name: BMP2K
• UniProt ID: BMP2K_HUMAN
• PDB ID: 4W9W; 4W9X; 5I3O; 5I3R; 5IKW
• EC Number: 2.7.11.1
• Pfam ID: PF15282 ; PF00069
• Sequence:
  MKKFSRMPKSEGGSGGGAAGGGAGGAGAGAGCGSGGSSVGVRVFAVGRHQVTLEESLAEG
  GFSTVFLVRTHGGIRCALKRMYVNNMPDLNVCKREITIMKELSGHKNIVGYLDCAVNSIS
  DNVWEVLILMEYCRAGQVVNQMNKKLQTGFTEPEVLQIFCDTCEAVARLHQCKTPIIHRD
  LKVENILLNDGGNYVLCDFGSATNKFLNPQKDGVNVVEEEIKKYTTLSYRAPEMINLYGG
  KPITTKADIWALGCLLYKLCFFTLPFGESQVAICDGNFTIPDNSRYSRNIHCLIRFMLEP
  DPEHRPDIFQVSYFAFKFAKKDCPVSNINNSSIPSALPEPMTASEAAARKSQIKARITDT
  IGPTETSIAPRQRPKANSATTATPSVLTIQSSATPVKVLAPGEFGNHRPKGALRPGNGPE
  ILLGQGPPQQPPQQHRVLQQLQQGDWRLQQLHLQHRHPHQQQQQQQQQQQQQQQQQQQQQ
  QQQQQQHHHHHHHHLLQDAYMQQYQHATQQQQMLQQQFLMHSVYQPQPSASQYPTMMPQY
  QQAFFQQQMLAQHQPSQQQASPEYLTSPQEFSPALVSYTSSLPAQVGTIMDSSYSANRSV
  ADKEAIANFTNQKNISNPPDMSGWNPFGEDNFSKLTEEELLDREFDLLRSNRLEERASSD
  KNVDSLSAPHNHPPEDPFGSVPFISHSGSPEKKAEHSSINQENGTANPIKNGKTSPASKD
  QRTGKKTSVQGQVQKGNDESESDFESDPPSPKSSEEEEQDDEEVLQGEQGDFNDDDTEPE
  NLGHRPLLMDSEDEEEEEKHSSDSDYEQAKAKYSDMSSVYRDRSGSGPTQDLNTILLTSA
  QLSSDVAVETPKQEFDVFGAVPFFAVRAQQPQQEKNEKNLPQHRFPAAGLEQEEFDVFTK
  APFSKKVNVQECHAVGPEAHTIPGYPKSVDVFGSTPFQPFLTSTSKSESNEDLFGLVPFD
  EITGSQQQKVKQRSLQKLSSRQRRTKQDMSKSNGKRHHGTPTSTKKTLKPTYRTPERARR
  HKKVGRRDSQSSNEFLTISDSKENISVALTDGKDRGNVLQPEESLLDPFGAKPFHSPDLS
  WHPPHQGLSDIRADHNTVLPGRPRQNSLHGSFHSADVLKMDDFGAVPFTELVVQSITPHQ
  SQQSQPVELDPFGAAPFPSKQ
• Function: May be involved in osteoblast differentiation.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

4 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 BMP-2-inducible protein kinase (BMP2K).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of BMP-2-inducible protein kinase (BMP2K).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BMP-2-inducible protein kinase (BMP2K).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of BMP-2-inducible protein kinase (BMP2K).	[17]

18 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 BMP-2-inducible protein kinase (BMP2K).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BMP-2-inducible protein kinase (BMP2K).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of BMP-2-inducible protein kinase (BMP2K).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of BMP-2-inducible protein kinase (BMP2K).	[5]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of BMP-2-inducible protein kinase (BMP2K).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of BMP-2-inducible protein kinase (BMP2K).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of BMP-2-inducible protein kinase (BMP2K).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of BMP-2-inducible protein kinase (BMP2K).	[9]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of BMP-2-inducible protein kinase (BMP2K).	[10]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of BMP-2-inducible protein kinase (BMP2K).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of BMP-2-inducible protein kinase (BMP2K).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of BMP-2-inducible protein kinase (BMP2K).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of BMP-2-inducible protein kinase (BMP2K).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of BMP-2-inducible protein kinase (BMP2K).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BMP-2-inducible protein kinase (BMP2K).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of BMP-2-inducible protein kinase (BMP2K).	[19]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of BMP-2-inducible protein kinase (BMP2K).	[20]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of BMP-2-inducible protein kinase (BMP2K).	[6]

References

• [1] 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.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [10] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [11] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [12] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] 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.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] 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.
• [17] 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.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.