Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8KME51)

• DOT Name: Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B)
• Synonyms: EC 2.7.11.1; MAD3/BUB1-related protein kinase; hBUBR1; Mitotic checkpoint kinase MAD3L; Protein SSK1
• Gene Name: BUB1B
• Related Disease:
  Acute myelogenous leukaemia
  Mosaic variegated aneuploidy syndrome 1
  Adenocarcinoma
  Adenoma
  Adult glioblastoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Dandy-Walker syndrome
  Embryonal neoplasm
  Esophageal squamous cell carcinoma
  Fetal growth restriction
  Gastric cancer
  Germ cell tumor
  Glioblastoma multiforme
  Hutchinson-Gilford progeria syndrome
  Hydrocephalus
  Isolated congenital microcephaly
  Lung cancer
  Lung carcinoma
  Malignant neoplasm
  Melanoma
  Metastatic malignant neoplasm
  Microlissencephaly
  Neoplasm
  Obesity
  Pancreatic cancer
  Renal cell carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Trichohepatoenteric syndrome
  Wilms tumor
  Epithelial ovarian cancer
  Rhabdomyosarcoma
  Mosaic variegated aneuploidy syndrome
  Aplasia cutis congenita
  Cataract
  Corpus callosum, agenesis of
  High blood pressure
  Premature aging syndrome
  Prostate cancer
  Prostate carcinoma
• UniProt ID: BUB1B_HUMAN
• PDB ID: 2WVI; 3SI5; 4GGD; 5JJA; 5K6S; 5KHU; 5LCW; 5SWF; 6TLJ
• EC Number: 2.7.11.1
• Pfam ID: PF08311
• Sequence:
  MAAVKKEGGALSEAMSLEGDEWELSKENVQPLRQGRIMSTLQGALAQESACNNTLQQQKR
  AFEYEIRFYTGNDPLDVWDRYISWTEQNYPQGGKESNMSTLLERAVEALQGEKRYYSDPR
  FLNLWLKLGRLCNEPLDMYSYLHNQGIGVSLAQFYISWAEEYEARENFRKADAIFQEGIQ
  QKAEPLERLQSQHRQFQARVSRQTLLALEKEEEEEVFESSVPQRSTLAELKSKGKKTARA
  PIIRVGGALKAPSQNRGLQNPFPQQMQNNSRITVFDENADEASTAELSKPTVQPWIAPPM
  PRAKENELQAGPWNTGRSLEHRPRGNTASLIAVPAVLPSFTPYVEETARQPVMTPCKIEP
  SINHILSTRKPGKEEGDPLQRVQSHQQASEEKKEKMMYCKEKIYAGVGEFSFEEIRAEVF
  RKKLKEQREAELLTSAEKRAEMQKQIEEMEKKLKEIQTTQQERTGDQQEETMPTKETTKL
  QIASESQKIPGMTLSSSVCQVNCCARETSLAENIWQEQPHSKGPSVPFSIFDEFLLSEKK
  NKSPPADPPRVLAQRRPLAVLKTSESITSNEDVSPDVCDEFTGIEPLSEDAIITGFRNVT
  ICPNPEDTCDFARAARFVSTPFHEIMSLKDLPSDPERLLPEEDLDVKTSEDQQTACGTIY
  SQTLSIKKLSPIIEDSREATHSSGFSGSSASVASTSSIKCLQIPEKLELTNETSENPTQS
  PWCSQYRRQLLKSLPELSASAELCIEDRPMPKLEIEKEIELGNEDYCIKREYLICEDYKL
  FWVAPRNSAELTVIKVSSQPVPWDFYINLKLKERLNEDFDHFCSCYQYQDGCIVWHQYIN
  CFTLQDLLQHSEYITHEITVLIIYNLLTIVEMLHKAEIVHGDLSPRCLILRNRIHDPYDC
  NKNNQALKIVDFSYSVDLRVQLDVFTLSGFRTVQILEGQKILANCSSPYQVDLFGIADLA
  HLLLFKEHLQVFWDGSFWKLSQNISELKDGELWNKFFVRILNANDEATVSVLGELAAEMN
  GVFDTTFQSHLNKALWKVGKLTSPGALLFQ
• Function: Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression.
• Tissue Specificity: Highly expressed in thymus followed by spleen. Preferentially expressed in tissues with a high mitotic index.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway:
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)
  Cdc20 (R-HSA-174184)
  APC/C (R-HSA-176409)
  APC-Cdc20 mediated degradation of Nek2A (R-HSA-179409)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Inactivation of APC/C via direct inhibition of the APC/C complex (R-HSA-141430)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Mosaic variegated aneuploidy syndrome 1	DISOV0CG	Definitive	Autosomal recessive	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Adenoma	DIS78ZEV	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[10]
Dandy-Walker syndrome	DIS4HC6W	Strong	Biomarker	[11]
Embryonal neoplasm	DIS5MQSB	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Fetal growth restriction	DIS5WEJ5	Strong	Genetic Variation	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Germ cell tumor	DIS62070	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[16]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Biomarker	[17]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[18]
Isolated congenital microcephaly	DISUXHZ6	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Altered Expression	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[19]
Malignant neoplasm	DISS6SNG	Strong	Genetic Variation	[11]
Melanoma	DIS1RRCY	Strong	Biomarker	[20]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[8]
Microlissencephaly	DISUCKNT	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[22]
Obesity	DIS47Y1K	Strong	Biomarker	[23]
Pancreatic cancer	DISJC981	Strong	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[7]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[25]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[4]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[4]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[26]
Wilms tumor	DISB6T16	Strong	Genetic Variation	[27]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[28]
Rhabdomyosarcoma	DISNR7MS	Moderate	Autosomal recessive	[29]
Mosaic variegated aneuploidy syndrome	DIS5QTMU	Supportive	Autosomal dominant	[21]
Aplasia cutis congenita	DISMDAYM	Limited	Biomarker	[30]
Cataract	DISUD7SL	Limited	Biomarker	[31]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[30]
High blood pressure	DISY2OHH	Limited	Biomarker	[32]
Premature aging syndrome	DIS51AGT	Limited	Biomarker	[33]
Prostate cancer	DISF190Y	Limited	Biomarker	[34]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[34]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B) affects the response to substance of Paclitaxel.	[75]
Docetaxel	DMDI269	Approved	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B) affects the response to substance of Docetaxel.	[75]

43 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 Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[42]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[45]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[46]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[47]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[41]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[48]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[49]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[50]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[51]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[52]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[53]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[54]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[55]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[56]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[57]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[58]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[59]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[42]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[60]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[54]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[62]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[63]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[64]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[65]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[67]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[68]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[69]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[70]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[71]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[54]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[72]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[73]
Choline	DM5D9YK	Investigative	Choline affects the expression of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[74]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the phosphorylation of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B).	[66]

References

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